Oncolytic Virotherapy
Oncolytic Viruses
Myxoma virus
Adenoviridae
Vesiculovirus
Virus Replication
Xenograft Model Antitumor Assays
Vaccinia virus
Mice, Nude
Neoplasms
Vesicular stomatitis Indiana virus
Genetic Vectors
Combined Modality Therapy
H-1 parvovirus
Adenovirus E1A Proteins
Genetic Therapy
Measles virus
Glioma
Cytopathogenic Effect, Viral
Combination effect of oncolytic adenovirotherapy and TRAIL gene therapy in syngeneic murine breast cancer models. (1/727)
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene therapy and oncolytic adenovirotherapy have been investigated extensively in xenografic human tumor models established in immunocompromised nude mice. However, the effects of these therapies on syngeneic murine tumors in immunocompetent settings were not well documented. We hypothesized that TRAIL gene therapy used with an oncolytic adenovirus would overcome the weaknesses of the two therapies used individually. In this study, we evaluated the antitumor effects of an oncolytic adenovirus, Delta24, in both human and murine breast cancer cell lines. We also analyzed the effects of TRAIL gene therapy combined with oncolytic virotherapy in these cancer cells. Our results showed that Delta24 can replicate and help the E1-deleted adenovector replicate in murine cancer cells. We also found that these two therapies combined had greater antitumor activity than either one alone in both human and murine breast cancer cells lines and in the syngeneic breast cancer models established in immunocompetent mice. Moreover, Delta24 virotherapy alone and combined with TRAIL gene therapy dramatically reduced the spontaneous liver metastasis that originated in the subcutaneous 4T1 tumor established in Balb/c mice. These findings provide important considerations in the development and preclinical assessments of oncolytic virotherapy. (+info)Radiation therapy potentiates effective oncolytic viral therapy in the treatment of lung cancer. (2/727)
BACKGROUND: Replication-competent oncolytic herpes simplex viruses with deletion of the gamma(1)34.5 gene preferentially replicate in and kill malignant cells. The gamma(1)34.5 gene codes for ICP 34.5, a protein that enhances viral replication, and is homologous to growth arrest and DNA damage protein 34 (GADD34), a radiation-inducible DNA repair gene. We hypothesized that radiation therapy may potentiate efficacy of oncolytic viral therapy by upregulating GADD34 and promoting viral replication. METHODS: The A549 and H1299 lung cancer cell lines were infected with NV1066, an oncolytic herpes simplex virus, at multiplicities of infection (number of viral particles per tumor cell) of 0.1 to 0.5 in vitro with radiation (2 to 10 Gy) or without radiation. Viral replication was determined by plaque assay, cell-to-cell spread was determined by flow cytometry, cell kill was determined by lactate dehydrogenase assay, and GADD34 induction was determined by real-time reverse transcription-polymerase chain reaction and Western blot method. Evidence of synergistic cytotoxicity dependence with GADD34 induction is further confirmed by small inhibitory RNA inhibition of GADD34 expression. RESULTS: Using both the isobologram method and combination index method of Chou and Talalay, significant synergism was demonstrated between radiation therapy and NV1066 both in vitro and in vivo. As a result of such synergism, a dose reduction for each agent (2- to 6,000-fold) can be accomplished for a wide range of therapeutic effect levels without sacrificing tumor cell kill. This effect is correlated with increased GADD34 expression and inhibited by transfection of small inhibitory RNA directed against GADD34. CONCLUSIONS: These data provide the cellular basis for the clinical investigation of combined use of radiation therapy with oncolytic herpes simplex virus therapy in the treatment of lung cancer to achieve synergistic efficacy while minimizing dosage and toxicity. (+info)Myxoma virus is a novel oncolytic virus with significant antitumor activity against experimental human gliomas. (3/727)
Myxoma virus, a poxvirus previously considered rabbit specific, can replicate productively in a variety of human tumor cells in culture. The purpose of this study was to determine if there was efficacy or toxicities of this oncolytic virus against experimental models of human malignant gliomas in vitro, in vivo, and ex vivo in malignant glioma specimens. In vitro, the majority of glioma cell lines tested (7 of 8, 87.5%) were fully permissive for myxoma virus replication and killed by infection. In vivo, intracerebral (i.c.) myxoma virus inoculation was well tolerated and produced only minimal focal inflammatory changes at the site of viral inoculation. U87 and U251 orthotopic xenograft models were used to assess myxoma virus efficacy in vivo. A single intratumoral injection of myxoma virus dramatically prolonged median survival compared with treatment with UV-inactivated myxoma virus. Median survival was not reached in myxoma virus-treated groups versus 47.3 days (U87; P = 0.0002) and 50.7 days (U251; P = 0.0027) in UV-inactivated myxoma virus-treated groups. Most myxoma virus-treated animals (12 of 13, 92%) were alive and apparently "cured" when the experiment was finished (>130 days). Interestingly, we found a selective and long-lived myxoma virus infection in gliomas in vivo. This is the first demonstration of the oncolytic activity of myxoma virus in vivo. The nonpathogenic nature of myxoma virus outside of the rabbit host, its capacity to be genetically modified, its ability to produce a long-lived infection in human tumor cells, and the lack of preexisting antibodies in the human population suggest that myxoma virus may be an attractive oncolytic agent against human malignant glioma. (+info)The enhanced tumor selectivity of an oncolytic vaccinia lacking the host range and antiapoptosis genes SPI-1 and SPI-2. (4/727)
The ability of cancer cells to evade apoptosis may permit survival of a recombinant vaccinia lacking antiapoptotic genes in cancer cells compared with normal cells. We have explored the deletion of two vaccinia virus host range/antiapoptosis genes, SPI-1 and SPI-2, for their effects on the viral replication and their ability to induce cell death in infected normal and transformed cells in vitro. Indeed, in three paired normal and transformed cell types, the SPI-1 and SPI-2 gene-deleted virus (vSP) preferentially replicates in transformed cells or p53-null cells when compared with their normal counterparts. This selectivity may be derived from the fact that vSP-infected normal cells died faster than infected cancer cells. A fraction of infected cells died with evidence of necrosis as shown by both flow cytometry and detection of high-mobility group B1 protein released from necrotic cells into the culture supernatant. When administered to animals, vSP retains full ability to replicate in tumor tissues, whereas replication in normal tissues is greatly diminished. In a model of viral pathogenesis, mice treated with vSP survived substantially longer when compared with mice treated with the wild-type virus. The mutant virus vSP displayed significant antitumoral effects in an MC38 s.c. tumor model in both nude (P < 0.001) and immunocompetent mice (P < 0.05). We conclude that this recombinant vaccinia vSP shows promise for oncolytic virus therapy. Given its enhanced tumor selectivity, improved safety profile, and substantial oncolytic effects following systemic delivery in murine models, it should also serve as a useful vector for tumor-directed gene therapy. (+info)Cisplatin-induced GADD34 upregulation potentiates oncolytic viral therapy in the treatment of malignant pleural mesothelioma. (5/727)
BACKGROUND: NV1066, a replication-competent oncolytic herpes simplex virus type 1 (HSV-1) attenuated by a deletion in the gene gamma(1)34.5, preferentially replicates in and kills malignant cells. gamma(1)34.5 encodes ICP34.5, a viral protein essential for productive replication, which has homology with mammalian stress response induced GADD34 (growth arrest and DNA damage-inducible protein). We hypothesized that cisplatin upregulates GADD34 expression, which enhances NV1066 replication and oncolysis. METHODS: Ten human malignant pleural mesothelioma (MPM) cell lines were infected with NV1066 at multiplicities of infection (MOI; ratio of viral particles per tumor cell) 0.005 to 0.8 in vitro, with and without cisplatin (1 to 4 microM). In the MPM cell line VAMT, viral replication was determined by plaque assay, cell kill by lactate dehydrogenase assay, and GADD34 induction by quantitative RT-PCR and Western blot. Synergistic efficacy was confirmed by the isobologram and combination index methods of Chou-Talalay. GADD34 upregulation by cisplatin was inhibited with GADD34 siRNA to further confirm the synergistic efficacy dependence with GADD34. RESULTS: Combination therapy with NV1066 and cisplatin showed strong synergism in epithelioid (H-2452, H-Meso), sarcomatoid (H-2373, H-28), and biphasic (JMN, Meso-9, MSTO-211H) MPM cell lines, and an additive effect in others. In VAMT cells combination therapy enhanced viral replication 4 to 11-fold (p < 0.01) and cell kill 2 to 3-fold (p < 0.01). Significant dose reductions for both agents (2 to 600-fold) were achieved over a wide range of therapeutic-effect levels (LD50-LD99) without compromising cell kill. Synergistic cytotoxicity correlated with GADD34 upregulation (2 to 4-fold, p < 0.01) and was eliminated following transfection with GADD34 siRNA. CONCLUSION: Cisplatin-induced GADD34 expression selectively enhanced the cytotoxicity of the gamma(1)34.5-deficient oncolytic virus, NV1066. This provides a cellular basis for combination therapy with cisplatin and NV1066 to treat MPM and achieve synergistic efficacy, while minimizing dosage and toxicity. (+info)Triple gene-deleted oncolytic herpes simplex virus vector double-armed with interleukin 18 and soluble B7-1 constructed by bacterial artificial chromosome-mediated system. (6/727)
Conditionally replicating herpes simplex virus type 1 (HSV-1) vectors are promising therapeutic agents for cancer. Certain antitumor functions may be added to oncolytic activities of recombinant HSV-1 vectors by inserting transgenes into the viral genome. Because conventional homologous recombination techniques had required time-consuming processes to create "armed" oncolytic HSV-1 vectors, we established an innovative construction system using bacterial artificial chromosome and two recombinase systems (Cre/loxP and FLPe/FRT). Using G47Delta, a safe and efficacious oncolytic HSV-1 with triple gene mutations, as the backbone, this system allowed a rapid generation of multiple vectors with desired transgenes inserted in the deleted ICP6 locus. Four oncolytic HSV-1 vectors, expressing murine interleukin 18 (mIL-18), soluble murine B7-1 [B7-1-immunoglobulin (B7-1-Ig)], both, or none, were created simultaneously within 3 months. In vitro, all newly created recombinant vectors exhibited virus yields and cytopathic effects similar to the parental G47Delta. In two immunocompetent mouse tumor models, TRAMP-C2 prostate cancer and Neuro2a neuroblastoma, the vector expressing both mIL-18 and B7-1-Ig showed a significant enhancement of antitumor efficacy via T-cell-mediated immune responses. The results show that "arming" with multiple transgenes can improve the efficacy of oncolytic HSV-1 vectors. The use of our system may facilitate the development and testing of various armed oncolytic HSV-1 vectors. (+info)CG0070, a conditionally replicating granulocyte macrophage colony-stimulating factor--armed oncolytic adenovirus for the treatment of bladder cancer. (7/727)
PURPOSE: The purpose of this study was to examine the tumor specificity, cytotoxicity, and granulocyte macrophage colony-stimulating factor expression of CG0070, a conditionally replicating oncolytic adenovirus, in human bladder transitional cell carcinoma (TCC) cell lines and determine its antitumor efficacy in bladder TCC tumor models. EXPERIMENTAL DESIGN: Virus yield and cytotoxicity assays were used to determine tumor specificity and virus replication-mediated cytotoxicity of CG0070 in a panel of human bladder TCC cell lines and primary cells in vitro. Two s.c. and one orthotopic bladder TCC xenograft tumor models were used to assess antitumor activity of CG0070. RESULTS: In a matched isogenic pair of cell lines with differing retinoblastoma (Rb) pathway status, CG0070 showed selective E1a and granulocyte macrophage colony-stimulating factor (GM-CSF) expression in Rb pathway-defective cells. CG0070 replicated in Rb-defective bladder TCC cell lines as efficiently as wild-type adenovirus but produced 100-fold less virus in normal human cells. CG0070 was up to 1,000-fold more cytotoxic in Rb pathway-defective bladder TCC cells in comparison with normal human cells. Antitumor activity of CG0070 was shown in two bladder TCC s.c. xenograft tumor models following intratumoral injections and intravesical treatment in an orthotopic xenograft tumor model when compared with PBS treatment. CONCLUSIONS: In vitro and in vivo studies showed the selective replication, cytotoxicity, GM-CSF production, and antitumor efficacy of CG0070 in several bladder TCC models, suggesting a potential utility of this oncolytic agent for the treatment of bladder cancer. Further studies are warranted to show the role of human GM-CSF in the antitumor efficacy of CG0070. (+info)Activated MEK suppresses activation of PKR and enables efficient replication and in vivo oncolysis by Deltagamma(1)34.5 mutants of herpes simplex virus 1. (8/727)
Herpes simplex virus mutants lacking the gamma(1)34.5 gene are not destructive to normal tissues but are potent cytolytic agents in human tumor cells in which the activation of double-stranded RNA-dependent protein kinase (PKR) is suppressed. Thus, replication of a Deltagamma(1)34.5 mutant (R3616) in 12 genetically defined cancer cell lines correlates with suppression of PKR but not with the genotype of RAS. Extensive analyses of two cell lines transduced with either dominant negative MEK (dnMEK) or constitutively active MEK (caMEK) indicated that in R3616 mutant-infected cells dnMEK enabled PKR activation and decreased virus yields, whereas caMEK suppressed PKR and enabled better viral replication and cell destruction in transduced cells in vitro or in mouse xenografts. The results indicate that activated MEK mediates the suppression of PKR and that the status of MEK predicts the ability of Deltagamma(1)34.5 mutant viruses to replicate in and destroy tumor cells. (+info)Oncolytic virotherapy is a type of cancer treatment that uses genetically modified viruses to selectively infect and destroy cancer cells, while leaving healthy cells unharmed. The virus used in oncolytic virotherapy can replicate inside cancer cells, causing them to rupture and release new viruses that can then infect nearby cancer cells.
The process continues in a cascading manner, leading to the destruction of many cancer cells in the treated area. Additionally, some oncolytic viruses can also stimulate an immune response against cancer cells, further enhancing their therapeutic effect. Oncolytic virotherapy is still an experimental treatment approach and is being studied in clinical trials for various types of cancer.
Oncolytic viruses are a type of viruses that preferentially infect and kill cancer cells, while leaving normal cells relatively unharmed. These viruses can replicate inside the cancer cells, causing them to rupture and ultimately leading to their death. The release of new virus particles from the dead cancer cells allows the infection to spread to nearby cancer cells, resulting in a potential therapeutic effect.
Oncolytic viruses can be genetically modified to enhance their ability to target specific types of cancer cells and to increase their safety and efficacy. They may also be used in combination with other cancer therapies, such as chemotherapy or radiation therapy, to improve treatment outcomes. Oncolytic virus therapy is a promising area of cancer research, with several clinical trials underway to evaluate its potential benefits for patients with various types of cancer.
Myxoma virus (MYXV) is a member of the Poxviridae family, specifically in the Leporipoxvirus genus. It is a double-stranded DNA virus that naturally infects European rabbits (Oryctolagus cuniculus) and causes a fatal disease called myxomatosis. The virus is transmitted through insect vectors such as mosquitoes and fleas, and it replicates in the cytoplasm of infected cells.
Myxoma virus has been studied extensively as a model organism for viral pathogenesis and host-pathogen interactions. It has also been explored as a potential oncolytic virus for cancer therapy due to its ability to selectively infect and kill certain types of cancer cells while leaving normal cells unharmed. However, it is important to note that the use of Myxoma virus in humans is still experimental and requires further research and development before it can be considered safe and effective for therapeutic purposes.
Adenoviridae is a family of viruses that includes many species that can cause various types of illnesses in humans and animals. These viruses are non-enveloped, meaning they do not have a lipid membrane, and have an icosahedral symmetry with a diameter of approximately 70-90 nanometers.
The genome of Adenoviridae is composed of double-stranded DNA, which contains linear chromosomes ranging from 26 to 45 kilobases in length. The family is divided into five genera: Mastadenovirus, Aviadenovirus, Atadenovirus, Siadenovirus, and Ichtadenovirus.
Human adenoviruses are classified under the genus Mastadenovirus and can cause a wide range of illnesses, including respiratory infections, conjunctivitis, gastroenteritis, and upper respiratory tract infections. Some serotypes have also been associated with more severe diseases such as hemorrhagic cystitis, hepatitis, and meningoencephalitis.
Adenoviruses are highly contagious and can be transmitted through respiratory droplets, fecal-oral route, or by contact with contaminated surfaces. They can also be spread through contaminated water sources. Infections caused by adenoviruses are usually self-limiting, but severe cases may require hospitalization and supportive care.
Vesiculovirus is a genus of enveloped, negative-stranded RNA viruses in the family Rhabdoviridae. They are known to cause vesicular diseases (hence the name) in both animals and humans, characterized by the formation of blisters or vesicles on the skin. The most well-known member of this genus is the vesicular stomatitis virus (VSV), which primarily affects cattle, horses, and pigs, causing oral and foot lesions. However, VSV can also infect humans, resulting in a flu-like illness. Other members of the Vesiculovirus genus include the Isfahan virus, Chandipura virus, and the Piry virus. These viruses are transmitted through insect vectors such as mosquitoes and sandflies, and can cause significant economic losses in the agricultural industry.
Virus replication is the process by which a virus produces copies or reproduces itself inside a host cell. This involves several steps:
1. Attachment: The virus attaches to a specific receptor on the surface of the host cell.
2. Penetration: The viral genetic material enters the host cell, either by invagination of the cell membrane or endocytosis.
3. Uncoating: The viral genetic material is released from its protective coat (capsid) inside the host cell.
4. Replication: The viral genetic material uses the host cell's machinery to produce new viral components, such as proteins and nucleic acids.
5. Assembly: The newly synthesized viral components are assembled into new virus particles.
6. Release: The newly formed viruses are released from the host cell, often through lysis (breaking) of the cell membrane or by budding off the cell membrane.
The specific mechanisms and details of virus replication can vary depending on the type of virus. Some viruses, such as DNA viruses, use the host cell's DNA polymerase to replicate their genetic material, while others, such as RNA viruses, use their own RNA-dependent RNA polymerase or reverse transcriptase enzymes. Understanding the process of virus replication is important for developing antiviral therapies and vaccines.
A xenograft model antitumor assay is a type of preclinical cancer research study that involves transplanting human tumor cells or tissues into an immunodeficient mouse. This model allows researchers to study the effects of various treatments, such as drugs or immune therapies, on human tumors in a living organism.
In this assay, human tumor cells or tissues are implanted into the mouse, typically under the skin or in another organ, where they grow and form a tumor. Once the tumor has established, the mouse is treated with the experimental therapy, and the tumor's growth is monitored over time. The response of the tumor to the treatment is then assessed by measuring changes in tumor size or weight, as well as other parameters such as survival rate and metastasis.
Xenograft model antitumor assays are useful for evaluating the efficacy and safety of new cancer therapies before they are tested in human clinical trials. They provide valuable information on how the tumors respond to treatment, drug pharmacokinetics, and toxicity, which can help researchers optimize dosing regimens and identify potential side effects. However, it is important to note that xenograft models have limitations, such as differences in tumor biology between mice and humans, and may not always predict how well a therapy will work in human patients.
Vaccinia virus is a large, complex DNA virus that belongs to the Poxviridae family. It is the virus used in the production of the smallpox vaccine. The vaccinia virus is not identical to the variola virus, which causes smallpox, but it is closely related and provides cross-protection against smallpox infection.
The vaccinia virus has a unique replication cycle that occurs entirely in the cytoplasm of infected cells, rather than in the nucleus like many other DNA viruses. This allows the virus to evade host cell defenses and efficiently produce new virions. The virus causes the formation of pocks or lesions on the skin, which contain large numbers of virus particles that can be transmitted to others through close contact.
Vaccinia virus has also been used as a vector for the delivery of genes encoding therapeutic proteins, vaccines against other infectious diseases, and cancer therapies. However, the use of vaccinia virus as a vector is limited by its potential to cause adverse reactions in some individuals, particularly those with weakened immune systems or certain skin conditions.
"Nude mice" is a term used in the field of laboratory research to describe a strain of mice that have been genetically engineered to lack a functional immune system. Specifically, nude mice lack a thymus gland and have a mutation in the FOXN1 gene, which results in a failure to develop a mature T-cell population. This means that they are unable to mount an effective immune response against foreign substances or organisms.
The name "nude" refers to the fact that these mice also have a lack of functional hair follicles, resulting in a hairless or partially hairless phenotype. This feature is actually a secondary consequence of the same genetic mutation that causes their immune deficiency.
Nude mice are commonly used in research because their weakened immune system makes them an ideal host for transplanted tumors, tissues, and cells from other species, including humans. This allows researchers to study the behavior of these foreign substances in a living organism without the complication of an immune response. However, it's important to note that because nude mice lack a functional immune system, they must be kept in sterile conditions and are more susceptible to infection than normal mice.
A cell line that is derived from tumor cells and has been adapted to grow in culture. These cell lines are often used in research to study the characteristics of cancer cells, including their growth patterns, genetic changes, and responses to various treatments. They can be established from many different types of tumors, such as carcinomas, sarcomas, and leukemias. Once established, these cell lines can be grown and maintained indefinitely in the laboratory, allowing researchers to conduct experiments and studies that would not be feasible using primary tumor cells. It is important to note that tumor cell lines may not always accurately represent the behavior of the original tumor, as they can undergo genetic changes during their time in culture.
Neoplasms are abnormal growths of cells or tissues in the body that serve no physiological function. They can be benign (non-cancerous) or malignant (cancerous). Benign neoplasms are typically slow growing and do not spread to other parts of the body, while malignant neoplasms are aggressive, invasive, and can metastasize to distant sites.
Neoplasms occur when there is a dysregulation in the normal process of cell division and differentiation, leading to uncontrolled growth and accumulation of cells. This can result from genetic mutations or other factors such as viral infections, environmental exposures, or hormonal imbalances.
Neoplasms can develop in any organ or tissue of the body and can cause various symptoms depending on their size, location, and type. Treatment options for neoplasms include surgery, radiation therapy, chemotherapy, immunotherapy, and targeted therapy, among others.
Vesicular stomatitis Indiana virus (VSIV) is a single-stranded, negative-sense RNA virus that belongs to the family Rhabdoviridae and genus Vesiculovirus. It is the causative agent of vesicular stomatitis (VS), a viral disease that primarily affects horses and cattle, but can also infect other species including swine, sheep, goats, and humans.
The virus is transmitted through direct contact with infected animals or their saliva, as well as through insect vectors such as black flies and sandflies. The incubation period for VS ranges from 2 to 8 days, after which infected animals develop fever, lethargy, and vesicular lesions in the mouth, nose, and feet. These lesions can be painful and may cause difficulty eating or walking.
In humans, VSIV infection is typically asymptomatic or causes mild flu-like symptoms such as fever, muscle aches, and headache. Occasionally, individuals may develop vesicular lesions on their skin or mucous membranes, particularly if they have had contact with infected animals.
Diagnosis of VSIV infection is typically made through virus isolation from lesion exudates or blood, as well as through serological testing. Treatment is generally supportive and aimed at relieving symptoms, as there are no specific antiviral therapies available for VS. Prevention measures include vaccination of susceptible animals, vector control, and biosecurity measures to prevent the spread of infection between animals.
A genetic vector is a vehicle, often a plasmid or a virus, that is used to introduce foreign DNA into a host cell as part of genetic engineering or gene therapy techniques. The vector contains the desired gene or genes, along with regulatory elements such as promoters and enhancers, which are needed for the expression of the gene in the target cells.
The choice of vector depends on several factors, including the size of the DNA to be inserted, the type of cell to be targeted, and the efficiency of uptake and expression required. Commonly used vectors include plasmids, adenoviruses, retroviruses, and lentiviruses.
Plasmids are small circular DNA molecules that can replicate independently in bacteria. They are often used as cloning vectors to amplify and manipulate DNA fragments. Adenoviruses are double-stranded DNA viruses that infect a wide range of host cells, including human cells. They are commonly used as gene therapy vectors because they can efficiently transfer genes into both dividing and non-dividing cells.
Retroviruses and lentiviruses are RNA viruses that integrate their genetic material into the host cell's genome. This allows for stable expression of the transgene over time. Lentiviruses, a subclass of retroviruses, have the advantage of being able to infect non-dividing cells, making them useful for gene therapy applications in post-mitotic tissues such as neurons and muscle cells.
Overall, genetic vectors play a crucial role in modern molecular biology and medicine, enabling researchers to study gene function, develop new therapies, and modify organisms for various purposes.
Combined modality therapy (CMT) is a medical treatment approach that utilizes more than one method or type of therapy simultaneously or in close succession, with the goal of enhancing the overall effectiveness of the treatment. In the context of cancer care, CMT often refers to the combination of two or more primary treatment modalities, such as surgery, radiation therapy, and systemic therapies (chemotherapy, immunotherapy, targeted therapy, etc.).
The rationale behind using combined modality therapy is that each treatment method can target cancer cells in different ways, potentially increasing the likelihood of eliminating all cancer cells and reducing the risk of recurrence. The specific combination and sequence of treatments will depend on various factors, including the type and stage of cancer, patient's overall health, and individual preferences.
For example, a common CMT approach for locally advanced rectal cancer may involve preoperative (neoadjuvant) chemoradiation therapy, followed by surgery to remove the tumor, and then postoperative (adjuvant) chemotherapy. This combined approach allows for the reduction of the tumor size before surgery, increases the likelihood of complete tumor removal, and targets any remaining microscopic cancer cells with systemic chemotherapy.
It is essential to consult with a multidisciplinary team of healthcare professionals to determine the most appropriate CMT plan for each individual patient, considering both the potential benefits and risks associated with each treatment method.
H-1 parvovirus is not typically used as a medical term. However, Parvovirus H-1 is a species of parvovirus that primarily infects canines and is not known to infect humans. It is associated with myocarditis (inflammation of the heart muscle) in dogs. Therefore, it's important to clarify that H-1 parvovirus is not related to human Parvovirus B19, which is a more common type of parvovirus that can cause disease in humans.
Adenovirus E1A proteins are the early region 1A proteins encoded by adenoviruses, a group of viruses that commonly cause respiratory infections in humans. The E1A proteins play a crucial role in the regulation of the viral life cycle and host cell response. They function as transcriptional regulators, interacting with various cellular proteins to modulate gene expression and promote viral replication.
There are two major E1A protein isoforms, 289R and 243R, which differ in their amino-terminal regions due to alternative splicing of the E1A mRNA. The 289R isoform contains an additional 46 amino acids at its N-terminus compared to the 243R isoform. Both isoforms share conserved regions, including a strong transcriptional activation domain and a binding domain for cellular proteins involved in transcriptional regulation, such as retinoblastoma protein (pRb) and p300/CBP.
The interaction between E1A proteins and pRb is particularly important because it leads to the release of E2F transcription factors, which are essential for the initiation of viral DNA replication. By binding and inactivating pRb, E1A proteins promote the expression of cell cycle-regulated genes that facilitate viral replication in dividing cells.
In summary, adenovirus E1A proteins are multifunctional regulatory proteins involved in the control of viral gene expression and host cell response during adenovirus infection. They manipulate cellular transcription factors and pathways to create a favorable environment for viral replication.
Genetic therapy, also known as gene therapy, is a medical intervention that involves the use of genetic material, such as DNA or RNA, to treat or prevent diseases. It works by introducing functional genes into cells to replace missing or faulty ones caused by genetic disorders or mutations. The introduced gene is incorporated into the recipient's genome, allowing for the production of a therapeutic protein that can help manage the disease symptoms or even cure the condition.
There are several approaches to genetic therapy, including:
1. Replacing a faulty gene with a healthy one
2. Inactivating or "silencing" a dysfunctional gene causing a disease
3. Introducing a new gene into the body to help fight off a disease, such as cancer
Genetic therapy holds great promise for treating various genetic disorders, including cystic fibrosis, muscular dystrophy, hemophilia, and certain types of cancer. However, it is still an evolving field with many challenges, such as efficient gene delivery, potential immune responses, and ensuring the safety and long-term effectiveness of the therapy.
Measles virus is a single-stranded, negative-sense RNA virus belonging to the genus Morbillivirus in the family Paramyxoviridae. It is the causative agent of measles, a highly contagious infectious disease characterized by fever, cough, runny nose, and a red, blotchy rash. The virus primarily infects the respiratory tract and then spreads throughout the body via the bloodstream.
The genome of the measles virus is approximately 16 kilobases in length and encodes for eight proteins: nucleocapsid (N), phosphoprotein (P), matrix protein (M), fusion protein (F), hemagglutinin (H), large protein (L), and two non-structural proteins, V and C. The H protein is responsible for binding to the host cell receptor CD150 (SLAM) and mediating viral entry, while the F protein facilitates fusion of the viral and host cell membranes.
Measles virus is transmitted through respiratory droplets and direct contact with infected individuals. The virus can remain airborne for up to two hours in a closed space, making it highly contagious. Measles is preventable through vaccination, which has led to significant reductions in the incidence of the disease worldwide.
A glioma is a type of tumor that originates from the glial cells in the brain. Glial cells are non-neuronal cells that provide support and protection for nerve cells (neurons) within the central nervous system, including providing nutrients, maintaining homeostasis, and insulating neurons.
Gliomas can be classified into several types based on the specific type of glial cell from which they originate. The most common types include:
1. Astrocytoma: Arises from astrocytes, a type of star-shaped glial cells that provide structural support to neurons.
2. Oligodendroglioma: Develops from oligodendrocytes, which produce the myelin sheath that insulates nerve fibers.
3. Ependymoma: Originate from ependymal cells, which line the ventricles (fluid-filled spaces) in the brain and spinal cord.
4. Glioblastoma multiforme (GBM): A highly aggressive and malignant type of astrocytoma that tends to spread quickly within the brain.
Gliomas can be further classified based on their grade, which indicates how aggressive and fast-growing they are. Lower-grade gliomas tend to grow more slowly and may be less aggressive, while higher-grade gliomas are more likely to be aggressive and rapidly growing.
Symptoms of gliomas depend on the location and size of the tumor but can include headaches, seizures, cognitive changes, and neurological deficits such as weakness or paralysis in certain parts of the body. Treatment options for gliomas may include surgery, radiation therapy, chemotherapy, or a combination of these approaches.
A Cytopathic Effect (CPE) is a visible change in the cell or group of cells due to infection by a pathogen, such as a virus. When the cytopathic effect is caused specifically by a viral infection, it is referred to as a "Viral Cytopathic Effect" (VCPE).
The VCPE can include various changes in the cell's morphology, size, and structure, such as rounding, shrinkage, multinucleation, inclusion bodies, and formation of syncytia (multinucleated giant cells). These changes are often used to identify and characterize viruses in laboratory settings.
The VCPE is typically observed under a microscope after the virus has infected cell cultures, and it can help researchers determine the type of virus, the degree of infection, and the effectiveness of antiviral treatments. The severity and timing of the VCPE can vary depending on the specific virus and the type of cells that are infected.
Vero cells are a line of cultured kidney epithelial cells that were isolated from an African green monkey (Cercopithecus aethiops) in the 1960s. They are named after the location where they were initially developed, the Vervet Research Institute in Japan.
Vero cells have the ability to divide indefinitely under certain laboratory conditions and are often used in scientific research, including virology, as a host cell for viruses to replicate. This allows researchers to study the characteristics of various viruses, such as their growth patterns and interactions with host cells. Vero cells are also used in the production of some vaccines, including those for rabies, polio, and Japanese encephalitis.
It is important to note that while Vero cells have been widely used in research and vaccine production, they can still have variations between different cell lines due to factors like passage number or culture conditions. Therefore, it's essential to specify the exact source and condition of Vero cells when reporting experimental results.
Oncolytic virus
Murine respirovirus
ECHO-7
Sedoreoviridae
Andrew Pecora
Virotherapy
Viralytics
Senecavirus
Poliovirus
PVSRIPO
Measles virus encoding the human thyroidal sodium iodide symporter
Cancer research
Melanoma
Talimogene laherparepvec
Oncolytic herpes virus
Measles
Herpes simplex virus
GL-ONC1
Oncolytic adenovirus
Glioblastoma
Nick Lemoine
Abscopal effect
Breast cancer
ONCOS-102
Genelux Corporation
Lisette de Pillis
Epithelioid sarcoma
Imugene
List of Dove Medical Press academic journals
Granulocyte-macrophage colony-stimulating factor
Oncolytic virotherapy Archives - GEN - Genetic Engineering and Biotechnology News
Delivery of oncolytic adenovirus into the nucleus of tumorigenic cells by tumor microparticles for virotherapy. | StemBook
Pevonedistat, a First in-class NEDD8-activating Enzyme Inhibitor, sensitizes cancer cells to VSV∆51 Oncolytic Virotherapy -...
Oncolytic Virotherapy Summit
7th Oncolytic Virotherapy Summit | Matica Biotechnology
Oncolytic Virotherapy in Veterinary Medicine - ELIAS Animal Health
Assistant Professor of oncolytic virotherapy - Jobs near me
Speakers, List of Speakers Speaking at Oncolytic Virotherapy Summit, Boston, USA
Supplementary Video 2 from A Multiscale Mathematical Model for Oncolytic Virotherapy
Oncolytic virus - Wikipedia
Oncolytic virotherapy evolved into the fourth generation as tumor immunotherapy | Journal of Translational Medicine | Full Text
A good start of immunotherapy in esophageal cancer
Intravenously injected Newcastle disease virus in non-human primates is safe to use for oncolytic virotherapy<...
Tropism ablation and stealthing of oncolytic adenovirus enhances systemic delivery to tumors and improves virotherapy of cancer...
Turning cold tumours hot: oncolytic virotherapy gets up close and personal with other therapeutics at the 11th Oncolytic Virus...
Ursolic acid and its nanoparticles are potentiators of oncolytic measles virotherapy against breast cancer cells<...
Universitätsklinikum Heidelberg: Seminars
Knowledge at MET
May 25, 2021 - EPOV Patrick Y. Wen - The ASCO Post
Is There a Cure for Cancer? Understanding the Latest Research
Pikor L[Author] - Search Results - PubMed
Heterogeneity and individualized treatment of microenvironment in glioblastoma (Review)
Malignant Melanoma Treatment & Management: Approach Considerations, Regional Lymph Node Dissection, Adjuvant Therapy
Frontiers | Oncolytic virus: A catalyst for the treatment of gastric cancer
Magiran | International Journal of Cancer Management، Volume:13 Issue: 9, Sep 2020
Oncolytic Adenoviral Delivery of an EGFR-Targeting T-cell Engager Improves Antitumor Efficacy | Cancer Research | American...
Localized Treatment with Oncolytic Adenovirus Delta-24-RGDOX Induces Systemic Immunity against Disseminated Subcutaneous and...
Events
Viruses | Free Full-Text | Dendritic Cells in Oncolytic Virus-Based Anti-Cancer Therapy
Viruses18
- In recent years, oncolytic viruses have been used in immunotherapeutic approaches to treat cancer. (eliasanimalhealth.com)
- Oncolytic viruses can kill tumor cells specifically or induce anticancer immune response. (figshare.com)
- Oncolytic viruses are thought not only to cause direct destruction of the tumour cells, but also to stimulate host anti-tumour immune system responses. (wikipedia.org)
- Oncolytic viruses also have the ability to affect the tumor micro-environment in multiple ways. (wikipedia.org)
- A number of viruses including adenovirus, reovirus, measles, herpes simplex, Newcastle disease virus, and vaccinia have been clinically tested as oncolytic agents. (wikipedia.org)
- Most current oncolytic viruses are engineered for tumour selectivity, although there are naturally occurring examples such as reovirus and the senecavirus, resulting in clinical trials. (wikipedia.org)
- As the technology to create a custom virus did not exist, all early efforts focused on finding natural oncolytic viruses. (wikipedia.org)
- The field of virotherapy was nearly abandoned for a time, as the technology required to modify viruses didn't exist whereas chemotherapy and radiotherapy technology enjoyed early success. (wikipedia.org)
- Oncolytic virotherapy (OVT) is a promising anti-tumor modality that utilizes oncolytic viruses (OVs) to preferentially attack cancers rather than normal tissues. (biomedcentral.com)
- OVT has its unique advantages and prospects, because oncolytic viruses (OVs) preferentially infect and replicate in tumor cells and destroy them, while leaving healthy cells largely untouched [ 7 ]. (biomedcentral.com)
- The first application of virotherapy with the engineered thymidine kinase (TK)-deficient herpes simplex viruses (HSV) was initiated in 1991 [ 10 ]. (biomedcentral.com)
- Oncolytic viruses (OVs) and phytochemical ursolic acid (UA) are two efficacious therapeutic candidates in development against breast cancer, the deadliest women's cancer worldwide. (tmu.edu.tw)
- This review integrates most experimental studies and clinical trials of various oncolytic viruses (OVs) in the diagnosis and treatment of GC. (frontiersin.org)
- Systemic delivery is a major goal in the field of oncolytic viruses. (karger.com)
- The team is working to enhance the potency of oncolytic virotherapy by using tumor-homing MSCs as carriers for delivery of viruses. (mayo.edu)
- Oncolytic viruses are biological agents that can exclusively eliminate cancer cells without harming normal cells. (thecurestartsnow.org)
- These viruses, called oncolytic viruses (OV), can be used as a form of-and catalyst for-immunotherapy. (accesshealthworldwide.org)
- First, the oncolytic viruses kill cancer cells directly when they infect these cells and cause them to burst. (accesshealthworldwide.org)
Adenovirus5
- Delivery of oncolytic adenovirus into the nucleus of tumorigenic cells by tumor microparticles for virotherapy. (stembook.org)
- An oncolytic adenovirus, a genetically modified adenovirus named H101, was approved in China in 2005 for the treatment of head and neck cancer. (wikipedia.org)
- Tropism ablation and stealthing of oncolytic adenovirus enhances systemic delivery to tumors and improves virotherapy of cancer. (ox.ac.uk)
- The oncolytic adenovirus ICOVIR-15K was engineered to express an EGFR-targeting BiTE (cBiTE) antibody under the control of the major late promoter, leading to generation of ICOVIR-15K-cBiTE, which retained its oncolytic properties in vitro . (aacrjournals.org)
- These peptides were then tested in our previously described oncolytic cancer vaccine platform PeptiCRAd, a vaccine platform that combines an immunogenic oncolytic adenovirus (OAd) coated with tumor antigen peptides. (elifesciences.org)
Measles virus4
- As a common strategy of enhancing monotherapeutic anticancer efficacy, we explored the combinatorial chemovirotherapeutic approach of combining oncolytic measles virus (MV), which targets the breast tumor marker Nectin-4, and the anticancer UA against breast adenocarcinoma. (tmu.edu.tw)
- Dr. Peng's team is currently working on the oncolytic measles virus (Edmonston strain) and vesicular stomatitis virus (Indiana strain). (mayo.edu)
- The virotherapy contains an attenuated oncolytic Edmonston (Ed) strain of measles virus encoding the human thyroidal sodium iodide symporter (MV-NIS) with the gene expression. (pharmaceutical-technology.com)
- The company develops two oncolytic virus platforms such as Vesicular Stomatitis Virus (VSV) and Measles Virus (MV-NIS). (pharmaceutical-technology.com)
20231
- Join us at 7th Oncolytic Virotherapy Summit to discuss your project and GMP availability for 2023! (maticabio.com)
Immunotherapy4
- There are a large number of clinical trials to study the application of immunotherapy such as immune checkpoint inhibitors, peptide vaccine, adoptive T cell transfer and oncolytic virus in esophageal cancer. (nih.gov)
- Oncolytic virus driven T-cell-based combination immunotherapy platform for colorectal cancer. (nih.gov)
- As an emerging cancer immunotherapy, oncolytic virotherapies (OVTs) can not only selectively lyse cancer cells, but also induce a systemic antitumor immune response. (frontiersin.org)
- These results confirmed the feasibility of applying the described pipeline for the selection of peptide candidates and generation of therapeutic oncolytic cancer vaccine, filling a gap in the field of cancer immunotherapy, and paving the way to translate our pipeline into human therapeutic approach. (elifesciences.org)
Therapeutic3
- Intravenous delivery of therapeutic virus particles remains a major goal for virotherapy of metastatic cancer. (ox.ac.uk)
- Here, we describe for the first time a streamlined pipeline for the generation of personalized cancer vaccines starting from the isolation and selection of the most immunogenic peptide candidates expressed on the tumor cells and ending in the generation of efficient therapeutic oncolytic cancer vaccines. (elifesciences.org)
- For these reasons, we hypothesize that the combination of Delta-24-RGDOX with inhibitors of IDO shall potentiate the therapeutic effect of oncolytic virotherapy for DIPG. (thecurestartsnow.org)
Immunotherapies2
- Genelux is a clinical-stage biopharmaceutical company focused on developing a pipeline of next-generation oncolytic immunotherapies for human patients suffering from aggressive and/or difficult-to-treat solid tumor types. (eliasanimalhealth.com)
- From targeted immunotherapies like oncolytic virotherapy (OV) and CAR-T cell therapy to the latest in genetic testing, here are the top innovations that have the potential to dramatically shift the paradigm of cancer care in the coming years. (accesshealthworldwide.org)
Clinical8
- Genelux has completed seven Phase I & II clinical trials in humans with their oncolytic virus technology, and they are currently enrolling a Phase III ovarian cancer trial. (eliasanimalhealth.com)
- From a clinical point of view, our findings indicate that a successful, single agent virotherapy requires a strong inhibition of the host immune response and the use of potent virus species with a high intratumoral mobility. (figshare.com)
- In 1996, the first approval was given in Europe for a clinical trial using the oncolytic virus HSV1716. (wikipedia.org)
- The conference brought together many of the major players in oncolytic virotherapy from all over the world, addressing all stages of research and development-from aspects of basic science and cellular immunology all the way through to early- and late-phase clinical trials. (ox.ac.uk)
- Today, both preclinical and early-stage clinical trials are intensively investigating the approach to improve oncolytic virotherapy. (slideshare.net)
- Oncolytic Virus to Target CD46 and SLC5A5 for Oncology is under clinical development by Vyriad and currently in Phase I for Atypical Teratoid Rhabdoid Tumor. (pharmaceutical-technology.com)
- Vyriad is a clinical stage bio-pharmaceutical company that develops viral-based novel oncolytic therapies for the treatment of cancer. (pharmaceutical-technology.com)
- The company also develops oncolytic virus in clinical phases of development. (pharmaceutical-technology.com)
Efficacy1
- "The G207 oncolytic herpes virus was tested in adults with gliomas with much less efficacy," Dr. Wen continued. (ascopost.com)
Vaccinia1
- ELIAS Animal Health previously announced it has in-licensed an oncolytic vaccinia virus treatment for pet animals from Genelux Corporation. (eliasanimalhealth.com)
Vesicular1
- Oncolytic vesicular stomatitis virus (VSV) can be delivered intravenously to target primary and metastatic lesions, but the interaction between human peripheral blood leukocytes (PBLs) and VSV remains poorly understood. (karger.com)
Genetically1
- Treatment with genetically engineered oncolytic herpes simplex virus type 1 (HSV-1) G207 alone or with radiation resulted in encouraging outcomes in a small study of pediatric patients with high-grade glioma. (ascopost.com)
Herpes1
- In 2015, talimogene laherparepvec (OncoVex, T-VEC), an oncolytic herpes virus which is a modified herpes simplex virus, became the first oncolytic virus to be approved for use in the United States and the European Union, for the treatment of advanced inoperable melanoma. (wikipedia.org)
Infect1
- An oncolytic virus is a virus that can infect and kill cancer cells, but not normal cells. (eliasanimalhealth.com)
Tumour1
- The treatment, called oncolytic virotherapy, involves injecting cancer lesions with a virus modified so it inhibits tumour growth and induces an anti-cancer immune response in the body. (liverpoolecho.co.uk)
Intravenously1
- In this study, we evaluated the toxicity, biodistribution and shedding of intravenously injected oncolytic NDVs in non-human primates (Macaca fascicularis). (eur.nl)
Vitro1
- Our findings revealed that in vitro co-treatment with UA synergistically potentiated the killing of human breast cancer cells by oncolytic MV, without UA interfering the various steps of the viral infection. (tmu.edu.tw)
Treatment3
- This oncolytic potentiation was partly attributed to the enhanced autophagic flux induced by the UA-NP and MV combined treatment. (tmu.edu.tw)
- Our study thus highlights the potential value of oncolytic MV and UA-based chemovirotherapy for further development as a treatment strategy against breast cancer, and the feasibility of employing nanoformulation to enhance UA's applicability. (tmu.edu.tw)
- Richardson, assistant professor of Neurological Surgery, joined the team of multidisciplinary neurooncology specialists and will create an independent research laboratory focusing on gene therapy and oncolytic virotherapy strategies for the treatment of adult and pediatric brain tumors. (iu.edu)
Oncology1
- GlobalData uses proprietary data and analytics to create drugs-specific PTSR and LoA in the Oncolytic Virus to Target CD46 and SLC5A5 for Oncology LoA Report. (pharmaceutical-technology.com)
Biological1
- Blood tests are necessary, easy-to-perform and low-cost alternatives for monitoring of oncolytic virotherapy and other biological therapies in translational research. (uni-wuerzburg.de)
Cancer cells2
- An oncolytic virus is a virus that preferentially infects and kills cancer cells. (wikipedia.org)
- Virally programmed extracellular vesicles sensitize cancer cells to oncolytic virus and small molecule therapy. (nih.gov)
Cancers1
- Early efforts also found that only certain cancers could be treated through virotherapy. (wikipedia.org)
Cells2
- Moreover, due to the discrete and stochastic nature of cells and their responses, an optimal range for viral cytotoxicity is predicted because the virotherapy fails if the oncolytic virus demands either a too short or a very large time to kill the tumor cell. (figshare.com)
- In this study, we tested the hypothesis that tumor-infiltrating T cells could be more effectively activated and redirected by oncolytic adenoviruses that were armed with bispecific T-cell-engager (BiTE) antibodies. (aacrjournals.org)
Infection1
- Efforts to treat cancer through immunisation or virotherapy (deliberate infection with a virus), began in the mid-20th century. (wikipedia.org)
Field1
- The Department of Biomedicine at Faculty of Health at Aarhus University invites applications for a position as Assistant Professor in the field of oncolytic virotherapy as per 1 January 2024 or as soon as possible thereafter. (jobs-near-me.eu)
Cell1
- Compared to the non-formulated UA, UA-NP exhibited improved drug dissolution property and similarly synergized with oncolytic MV in inducing apoptotic breast cancer cell death. (tmu.edu.tw)
Approach1
- The project is innovative in its approach because it counteracts an ad-hoc resistance mechanism to virotherapy identified in our laboratories that has not been examined previously. (thecurestartsnow.org)
Potential1
- Newcastle disease virus (NDV) is an avian pararnyxovirus with oncolytic potential. (eur.nl)
Close1
- Turning cold tumours hot: oncolytic virotherapy gets up close and personal with other therapeutics at the 11th Oncolytic Virus Conference. (ox.ac.uk)
Response1
- Even less information is available about the response to oncolytic virotherapy (T-VEC). (usz.ch)
Research1
- As Assistant Professor of oncolytic virotherapy your primary tasks will be research and research-based teaching. (jobs-near-me.eu)
Safety1
- Detailed preclinical information regarding the safety of Oncolytic NDV is scarce. (eur.nl)
Conference1
- The 11th International Oncolytic Virus Conference (IOVC) was held from April 9-12, 2018 in Oxford, UK. (ox.ac.uk)
Study1
- We discuss the implications of these results for our study and the Use of NDV for virotherapy. (eur.nl)