Adoptive transfer cells or tumor cells cells acquire antigens from tumors antigen of tumor. Medical search. Frequent questions

Nevertheless, ex vivo activation with cytokines can restore cytolytic activity of NK cells against GB, indicating that NK cells have potential for adoptive immunotherapy of GB if potent cytotoxicity can be maintained in vivo . (frontiersin.org)
Furthermore, similar to T cells, specific recognition and elimination of cancer cells by NK cells can be markedly enhanced through expression of chimeric antigen receptors (CARs), which provides an opportunity to generate NK-cell therapeutics of defined specificity for cancer immunotherapy. (frontiersin.org)
We then outline preclinical approaches that employ CAR-NK cells for GB immunotherapy, and give an overview on the ongoing clinical development of ErbB2 (HER2)-specific CAR-NK cells currently applied in a phase I clinical trial in glioblastoma patients. (frontiersin.org)
Immunotherapy protocols are designed to annihilate immune escape in cancer cells and restore elimination of cancer cells. (oaepublish.com)
Conclusions Our results demonstrate a novel way to use TLR agonists to improve immunotherapy and reveal a vital role for B cells in the generation of potent CD8 + T cell-based therapies. (bmj.com)
However, not all patients respond to immunotherapy, acquired resistance remains a challenge, and responses are poor in certain tumors which are considered to be immunologically cold. (biomedcentral.com)
This has led to the need for new immunotherapy-based approaches, including adoptive cell transfer (ACT), therapeutic vaccines, and novel immune checkpoint inhibitors. (biomedcentral.com)
The use of cell therapies, drivers of immune response, and trends in immunotherapy were the focus of the Immunotherapy Bridge (November 30th-December 1st, 2022), organized by the Fondazione Melanoma Onlus, Naples, Italy, in collaboration with the Society for Immunotherapy of Cancer. (biomedcentral.com)
This has resulted in the development of additional immunotherapy-based approaches, including adoptive cell transfer (ACT), therapeutic vaccines, and inhibitors of other immune checkpoints. (biomedcentral.com)
The use of cell therapies, drivers of immune response, and trends in immunotherapy were the focus of the Immunotherapy Bridge (November 30th-December 1st, 2022). (biomedcentral.com)
Cell-based therapy has expanded its influence in cancer immunotherapy, regenerative medicine, and tissue engineering. (biomedcentral.com)
In particular, stem cells, including mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), and induced pluripotent stem cells (iPSCs), and immune cells, such as T-cells and Natural Killer (NK) cells, have been favored candidates for regenerative medicine and cell-based cancer immunotherapy, respectively. (biomedcentral.com)
Unfortunately, these breakthrough discoveries in both regenerative medicine and cancer immunotherapy using cells as therapeutic reagents soon faced a common problem: the inability to control cellular functions to maximize the therapeutic benefits. (biomedcentral.com)
The developmental story of cell-based cancer immunotherapy is not so different from MSCs in regenerative medicine. (biomedcentral.com)
As shown by multiplex tissue immunofluorescence and intravital microscopy, combined immunotherapy treatments enhance T cell infiltration and the intratumoral performance of T lymphocytes. (unav.edu)
Breakthroughs in anti-tumor immunity have led to unprecedented advances in immunotherapy, yet it is now clear that the tumor microenvironment (TME) restrains immunity. (elifesciences.org)
Expanded understanding of the basic biology of T cell activation has enabled immunotherapy to combat cancer, and T cell metabolism now offers the opportunity to optimize and improve these therapeutic strategies. (elifesciences.org)
Finally, we will provide an overview of how utilizing an understanding of T cell metabolism may inform strategies to alter the TME or enhance T cell metabolism to strengthen the immunotherapy arsenal. (elifesciences.org)
Collectively, our results identify how and when to administer TLR agonists to augment T cell-based immunotherapy in the absence or presence of host preconditioning for treatment of advanced malignancies. (biomedcentral.com)
Is Novartis building a viable business model for adoptive immunotherapy for cancer? (biopharmconsortium.com)
This blog post, which was in part based on an article in the April 2011 issue of T he Scientist , described a treatment for metastatic melanoma known as adoptive cell transfer (ACT), or adoptive immunotherapy. (biopharmconsortium.com)
Research on the mechanistic basis of adoptive immunotherapy, as well as on means to improve ACT technologies, is ongoing, so there is the potential to improve the durable complete response rate further. (biopharmconsortium.com)
Thus only a handful of locations can bear the financial burden of administering adoptive immunotherapy. (biopharmconsortium.com)
Now comes an agreement (announced on August 6, 2012) between Novartis and the University of Pennsylvania (Penn) aimed at commercializing adoptive cellular immunotherapy. (biopharmconsortium.com)
The agreement is based on one of the improvements to ACT discussed in the December 2011 Nature cancer immunotherapy review , in which autologous T cells isolated from patient blood (not from tumors) are engineered with retroviral vectors carrying chimeric antigen receptors (CARs). (biopharmconsortium.com)
Defined immune thresholds for tumor protection and the factors affecting such thresholds have not well been investigated in cancer immunotherapy. (bmj.com)
2016). "Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses" Nat Med. (bioxcell.com)

In contrast to other cancers such as adenocarcinomas of the lung or melanoma, primary brain tumors like GB and low grade gliomas (LGG) are known as rather immunologically "cold" tumors, typically with low numbers of tumor-infiltrating lymphocytes (TILs) ( 4 ), and the mere amount of TILs is not associated with patient survival ( 5 ). (frontiersin.org)
Indeed, an increase in the recruitment of cytotoxic CD8 + T-lymphocytes into the tumor is mediated by chemokines such as C-C motif chemokine ligand 5, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL10 and is correlated to lower metastasis risk and better outcome for patients [ 1 - 3 ] [Figure 1] . (oaepublish.com)
Methods In this study we investigated how tumor-specific murine CD8 + T cells and human tumor infiltrating lymphocytes (TILs) are impacted when expanded ex vivo with the TLR9 agonist CpG. (bmj.com)
Although the efficacy of adoptive transfer of tumor infiltrating lymphocytes (TILs) was examined over several decades, genetically engineered T cells expressing chimeric antigen receptors (CARs) rapidly replaced the application of TILs due to their high specificity, non-MHC-restricted recognition of tumor antigen, superior potency, and improved in vivo persistency [ 9 , 13 , 14 ]. (biomedcentral.com)
This review will discuss the metabolic changes that drive T cells into different stages of their development and how the TME imposes barriers to the metabolism and activity of tumor infiltrating lymphocytes. (elifesciences.org)
Tumor-infiltrating lymphocyte (TIL) therapy is a type of adoptive cellular therapy by harvesting infiltrated lymphocytes from tumors, culturing and amplifying them in vitro and then infusing back to treat patients. (biomedcentral.com)
Currently, the most widely-used TIL production method is to isolate infiltrating lymphocytes from tumor tissues and then culture and expand these cells in vitro. (biomedcentral.com)
Tumor infiltrating lymphocytes (TILs) in a colorectal carcinoma. (biopharmconsortium.com)
Such cells are known as "tumor infiltrating lymphocytes" (TILs). (biopharmconsortium.com)
He or she then expands the numbers of the antitumor T lymphocytes in cell culture, using the T-cell growth factor, IL-2. (biopharmconsortium.com)
Despite the existence of a highly immunosuppressive tumor environment, adenovirus-infected cells can nonetheless be efficiently cleared by infiltrating cytotoxic T lymphocytes (CTL) without compromising tumor burden. (aacrjournals.org)
Activated γδ T cells exhibit strong cytotoxic activity and cytokine secretion functions and are effective antitumor lymphocytes with simple and direct recognition modes and rapid responses. (explorationpub.com)

Chimeric antigen receptor T (CART) cell therapy targeting the B cell specific differentiation antigen CD19 has shown clinical efficacy in a subset of relapsed/refractory (r/r) diffuse large B cell lymphoma (DLBCL) patients. (frontiersin.org)

The new incoming challenge is now therefore to overcome these resistance and new recent data presented epigenetic modifications as promising targets to restore anti-tumor immunity. (oaepublish.com)
Isolated B cells also imparted T cells with the CpG-associated phenotype and improved tumor immunity without the aid of additional antigen-presenting cells or other immune cells in the culture. (bmj.com)
As T cell metabolism dictates effector function, it is now apparent that the effect of cancer cell metabolism on the tumor microenvironment (TME) may impair anti-tumor immunity, and these new hallmarks of cancer are therefore inextricably linked. (elifesciences.org)
In contrast, ACT expands a patient's own T cells ex vivo to direct anti-tumor immunity when transfused back into the patient. (elifesciences.org)
On the other hand, other ligands, such as HLA, bind to inhibitory receptors NKG2A and killer immunoglobulin-like receptors (KIR) to inhibit NK cells, providing a form of protection for self-cells from innate immunity. (molcells.org)
To determine the mechanisms of how innate immune activation via lymphodepletion potentiated antitumor T cell immunity, we utilized the pmel-1 melanoma mouse model. (biomedcentral.com)
In addition, whereas weak pre-existing immunity did not alter the protective thresholds of the vaccine-specific T cell response following subsequent immunization with CMV-based vaccine vectors, strong pre-existing immunity inhibited the development of vaccine-induced T cells and their control on tumor progression. (bmj.com)
Therapeutic cancer vaccines aim to boost the natural immunity against transformed cancer cells, and a series of adjuvants and co-stimulatory molecules have been proposed to enhance the immune response against weak self-antigens expressed on cancer cells. (biomedcentral.com)
Alternatively, the adjuvant activity of CD1d-restricted invariant NKT cells (iNKT) on the innate and adaptive immunity is well demonstrated, and several CD1d glycolipid ligands are under pre-clinical and clinical evaluation. (biomedcentral.com)

NK cells contribute to cancer immune surveillance not only by their direct natural cytotoxicity which is triggered rapidly upon stimulation through germline-encoded cell surface receptors, but also by modulating T-cell mediated antitumor immune responses through maintaining the quality of dendritic cells and enhancing the presentation of tumor antigens. (frontiersin.org)
Adoptive cell therapy using engineered T-cell receptors (TCRs) targeting cancer-testis antigens, such as Melanoma-associated antigen 3 (MAGE-A3), is a potential approach for the treatment of NSCLC. (thno.org)
Further, inhibitory receptors present in the TME can inhibit T cell metabolism and alter T cell signaling both directly and through release of extracellular vesicles such as exosomes. (elifesciences.org)
Thus, the overall response of an NK cell depends on the balance of stimulating these different receptors. (molcells.org)

T cells expanded ex vivo from a CpG-treated culture demonstrated potent antitumor efficacy and prolonged persistence in vivo. (bmj.com)
Efficacy was dependent on the number of CD8+ T cells able to recognize tumor antigens that infiltrated the malignant tissue. (unav.edu)
Combining tumor-specific adoptive T cell therapy to the aCTLA-4/aPD1/rIL2 or aCTLA-4/aPD1/aCD137 reg-imens enhances efficacy in a synergistic manner. (unav.edu)
To this end, Dr. Rosenberg and others developed a "Young TIL" approach that rapidly expands TIL for administration without in vitro selection for tumor reactivity [ 8 ], which markedly improves the timeliness of TIL production as well as its survival and efficacy in vivo (Fig. 1 ). (biomedcentral.com)
Altogether, our study in mice demonstrates that αGC/CD1d-antitumor fusion protein greatly increases the efficacy of a therapeutic CpG-based cancer vaccine, first as an adjuvant during T cell priming and second, as a therapeutic agent to redirect immune responses to the tumor site. (biomedcentral.com)
According to current challenges, there is a need to explore innovative immunotherapies, maximize the tumor-killing efficacy of γδ T cells, and attenuate or eliminate tumor immunosuppression. (explorationpub.com)

While GB tumors are frequently infiltrated by natural killer (NK) cells, these are actively suppressed by the GB cells and the GB tumor microenvironment. (frontiersin.org)
Here, we discuss effects of the GB tumor microenvironment on NK-cell functionality, summarize early treatment attempts with ex vivo activated NK cells, and describe relevant CAR target antigens validated with CAR-T cells. (frontiersin.org)
Nevertheless, the composition of the immunologic tumor microenvironment undergoes changes upon radiotherapy, chemotherapy, or even after anti-angiogenic therapy ( 6 ). (frontiersin.org)
γδ T cells recruited into the tumor microenvironment can act as effector cells to mediate cancer immune surveillance. (explorationpub.com)
Therefore, an in-depth understanding of γδ T cells that play conflicting roles in the tumor microenvironment is necessary. (explorationpub.com)

Long-term studies on T cells in a cohort of patients vaccinated against yellow fever revealed that vaccine-induced CD8+ TSCM cells specific to yellow fever antigens were stably maintained for 25 years, capable of self-renewal ex vivo, and preserved surface markers and mRNA profiles closest to naïve T cells. (wikipedia.org)
TSCM are considered as a promising approach in immune cell therapy in cancers due to their high proliferation capacity, longevity and increased survival as well as more potent antitumor effects compared with Tcm and Tem in vivo. (wikipedia.org)
We posited that TLR agonists could be repurposed ex vivo to condition T cells with remarkable potency in vivo, circumventing TLR-related toxicity. (bmj.com)
These cells can be activated ex vivo to exhibit a potent antitumor effector function. (biomedcentral.com)
The study and/or manipulation of administered cells can potentially result in identification of the exact cell subpopulations and effector functions required for cancer regression in vivo. (biomedcentral.com)
Due to their secretory functions, differentiation capabilities, specific homing effects through chemotaxis, distinctive therapeutic potentials, and ex vivo expandability, cells have become an attractive reagent for advanced therapeutic strategies. (biomedcentral.com)
Notably, intratumoral injection of this cBiTE-expressing adenovirus increased the persistence and accumulation of tumor-infiltrating T cells in vivo , compared with the parental virus lacking such effects. (aacrjournals.org)

Our findings have immediate implications in the clinical treatment of advanced solid tumors. (bmj.com)
Its diverse TCR clonality, superior tumor-homing ability, and low off-target toxicity endow TIL therapy unique advantages in treating solid tumors compared with other adoptive cellular therapies. (biomedcentral.com)

A non-myeloablative lymphodepleting preparative regimen with 5Gy TBI prior to an ACT regimen can induce destruction of B16F10 melanoma in mice by removing cytokine sinks, depleting suppressive T reg cells, transiently ablating myeloid derived suppressor cells (MDSCs) and activating the innate immune system [ 11 ]. (biomedcentral.com)
In a clinical study of ACT published in 2011 , the treatment resulted in the disappearance of all tumors in 20/93 patients (21.5%) with advanced metastatic melanoma. (biopharmconsortium.com)
The cost of ACT is, however, much lower than a full course of other immunotherapies, such as the dendritic cell vaccine Provenge (which is not indicated for melanoma) or the immunotheraputic MAb drug ipilimumab, both of which cost approximately $120,000. (biopharmconsortium.com)
The resulting antitumor therapy is tested against established tumor grafts of B16 melanoma cells expressing human HER2 and ovalbumin. (biomedcentral.com)

Indeed, both DNA methylation and post-translational histone modifications have been described to regulate immune checkpoint inhibitor expression, tumor-associated antigen presentation or cancer cell editing by the immune system and therefore establishing epigenetic drugs as a potential complement to immunotherapies to improve their efficiency. (oaepublish.com)
We develop a multifocal HCC model to test immunotherapies by introducing c-myc using hydrodynamic gene transfer along with CRISPR-Cas9-mediated disruption of p53 in mouse hepatocytes. (unav.edu)
Two of the primary immunotherapies are immune checkpoint blockade (ICB) and adoptive cell transfer (ACT). (elifesciences.org)
Among PSCs, the donors available for induced pluripotent stem cells (iPSCs) are greatest, providing a potentially universal cell source for all types of cell therapies including cancer immunotherapies using natural killer (NK cells). (molcells.org)
There already exist several protocols to genetically modify and differentiate iPSCs into NK cells, and each has its own advantages with regards to immunotherapies. (molcells.org)
In this short review, we detail the benefits of using iPSCs in NK cell immunotherapies and discuss the challenges that must be overcome before this approach becomes mainstream in the clinic. (molcells.org)
Adoptive immunotherapies are still considered experimental, are not FDA-approved, and are not covered by third party payers. (biopharmconsortium.com)
Adoptive immunotherapies lack a clearly defined claim to intellectual property (IP), since the patient's own cells are not a "drug" to be patented. (biopharmconsortium.com)
Finally, it retrospectively analyze the activation strategies and clinical relevance of existing γδ T cell adoptive immunotherapies. (explorationpub.com)

There is also a need for rational combinations beyond interleukin (IL)-2 and programmed death (PD)-1/ cytotoxic T-lymphocyte-associated antigen (CTLA)-4 immune checkpoint blockade and to combat exhaustion and restore costimulatory functions, e.g., with gene-engineered or pharmacologic agent-treated TILs. (biomedcentral.com)
The preparative lymphodepletion treatment is associated with enhanced persistence of the transferred TILs. (biopharmconsortium.com)

Together with the transcriptome analysis of differentially expressed genes reflecting the relatedness of TSCM and Tn cells, these data support the existing hierarchical model of human T cell differentiation: naïve T cells (Tn) → stem cell like memory T cells (T scm) → central memory T cells (Tcm) → effector memory T cells (Tem) / effector T cells (Teff). (wikipedia.org)
Antigen presentation by the professional antigen-presenting cells (APCs) are normally recognized by immune cells via a surface T-cell receptor (TCR), leading to the induction of naive CD8 + T-cell clonal expansion and differentiation and finally resulting in the cell death of APCs. (oaepublish.com)
T cells must substantially increase nutrient uptake to mount a proper immune response and failure to obtain sufficient nutrients or engage the appropriate metabolic pathways can alter or prevent effector T cell differentiation and function. (elifesciences.org)
This review will discuss the metabolic adaptations necessary for T cells to meet changing biochemical needs throughout different stages of differentiation. (elifesciences.org)
Accordingly, scientists have developed protocols for the expansion, genetic modification and differentiation of stem cells to NK cells. (molcells.org)

CpG fostered the expansion of potent CD8 + T cells with the signature phenotype and antitumor ability via empowering a direct B-T cell interaction. (bmj.com)
Successful TIL therapy starts with the identification, enrichment, stimulation, and expansion of potent tumor-reactive T cells. (biomedcentral.com)
CD137 (4-1BB) is a member of the TNFR family that mediates potent T cell costimulatory signals upon ligation by CD137L or agonist monoclonal antibodies (mAbs). (unav.edu)
Upon mRNA intratumoral injections in the transplantable mouse cancer models CT26, MC38, and B16OVA, potent therapeutic effects were observed following repeated injections into the tumors. (unav.edu)
For instance, a peptide/CpG-based cancer vaccine has been evaluated in several clinical trials and was shown in pre-clinical studies to favor the expansion of effector T versus Tregs cells, resulting in a potent antitumor activity, as compared to other TLR ligands. (biomedcentral.com)

Specific tumor-associated antigens (TAAs) expressed by cancer cells can be identified by the immune system and results in the activation of immune system effectors and the consequent elimination of the cancer cells. (oaepublish.com)
Taking advantage of the diverse γδ TCR repertoire or other ligand-receptor interactions, γδ T cells can recognize a broad spectrum of tumor-associated antigens (TAAs) in a major histocompatibility complex (MHC)-independent manner, thereby activating downstream pleiotropic effects. (explorationpub.com)

CpG-conditioned CD8 + T cells acquired a unique proteomic signature hallmarked by an IL-2Rα high ICOS high CD39 low phenotype and an altered metabolic profile, all reliant on B cells transiently present in the culture. (bmj.com)
Transferred T cells that persist in the blood and form memory have a phenotype consistent with a less differentiated state (CD27/CD28/IL-7 receptor-α) [ 3 ]. (biomedcentral.com)
The timing of LPS administration and the requirement of individual components of the tripartite therapy were evaluated based on tumor growth and the phenotype of recovered splenocytes by flow cytometry. (biomedcentral.com)
The magnitude, kinetics and phenotype of the circulating tumor-specific CD8 + T cell response were determined. (bmj.com)

Univariate and multivariate regression analyses showed that low levels of differentiated CD3 + CD27 - CD28 - T cells (23.3 ± 19.3% versus 35.1 ± 18.0%) were independently associated with OR. (frontiersin.org)
Moreover, we found that sequentially administering LPS during or one day prior to ACT therapy compromised tumor regression. (biomedcentral.com)

Toll-like receptor (TLR) agonists can invigorate antitumor T cell responses when administered directly to patients, but these responses often coincide with toxicities. (bmj.com)
Microbial components, such as LPS, are key mediators of total body irradiation (TBI) enhancement, but our ability to strategically use these toll-like receptor (TLR) agonists to bolster the potency of T cell-based therapies for cancer remains elusive. (biomedcentral.com)
We have recently shown that the vaccine formulation, and in particular the presence of the Toll-like Receptor (TLR) agonist CpG, can significantly promote the maturation of pro-inflammatory DCs, which favors Type I T cell responses while restricting the expansion of Tregs [ 4 ]. (biomedcentral.com)
γδ T cells express unique T cell receptor (TCR) γ and TCR δ chains, with structural and functional heterogeneity. (explorationpub.com)

Examples of direct implication of epigenetic modifications in immune recognition of cancer cells. (oaepublish.com)
Importantly, T cells artificially expressing the MAGE-A3-Mp4 specific TCRs exhibited strong MAGE-A3+ tumor cell recognition and killing effect. (thno.org)
The traditional procedure of TIL production is assayed for specific tumor recognition and usually takes 6-8 weeks. (biomedcentral.com)
In addition to TLR ligands, CD1d-restricted invariant NKT (iNKT) cells have been shown to efficiently promote the transactivation of DCs through the CD40L-CD40 interaction upon recognition of the CD1d-glycolipid antigen complex by their semi-invariant TCR. (biomedcentral.com)

However, systematic analysis of T cell immune responses to MAGE-A3 antigen and corresponding antigen-specific TCR is still lacking. (thno.org)
Although immune checkpoint blockade (ICB) reinvigorates anti-tumor immune responses by disrupting co-inhibitory T-cell signaling, relapse frequently occurs after ICB treatment and acquired resistance often emergence after initial response [ 4 ]. (thno.org)
While the T cell precursor subset is known to play an important role in T cell responses, little is known about how or when these cells arise. (acir.org)
Background The capacity of cytomegalovirus (CMV) to elicit long-lasting strong T cell responses, and the ability to engineer the genome of this DNA virus positions CMV-based vaccine vectors highly suitable as a cancer vaccine platform. (bmj.com)
We here determined using CMV as a vaccine platform whether critical thresholds of vaccine-specific T cell responses can be established that relate to tumor protection, and which factors control such thresholds. (bmj.com)
However, low dose inoculations via the IP or SC route or IN vaccination elicited vaccine-induced CD8 + T cell responses that did not reach protective thresholds for tumor protection. (bmj.com)
Circulating and intratumoral NK and H-2Kb/OVA-specific CD8 responses are monitored, as well as the state of activation of dendritic cells (DC) with regard to activation markers and IL-12 secretion. (biomedcentral.com)
The enhanced innate and adaptive immune responses result in higher tumor inhibition that correlates with increased numbers of OVA-specific CTLs at the tumor site. (biomedcentral.com)
Taken together, this research supports an important role for early activity by Ly6G(+) cells in the generation of long-term PDT responses in mesothelioma, and it points to luminol chemiluminescence as a potentially useful approach for preclinical monitoring of neutrophil activation by PDT. (bioxcell.com)

TSCM infusion led to a more sustained reduction in tumor growth and correlated with a significant increase in overall survival of treated mice. (wikipedia.org)
We show that treatment of the mice with a combination of anti-CTLA-4 + anti-PD1 mAbs results in partial clearance of the tumor with an improvement in survival. (unav.edu)
B16F10-bearing mice were preconditioned with 5Gy TBI and given a tripartite ACT therapy (consisting of transferred pmel-1 CD8 + T cells, vaccination with fowlpox encoding gp100, and IL-2) along with TLR4 agonist LPS. (biomedcentral.com)
Finally, TBI was no longer needed to regress tumors in mice who were depleted of host CD4 + T cells, given a tripartite ACT regimen and then treated with low dose LPS. (biomedcentral.com)
transferred labeled TCR-transgenic CD8 + P14 T cells that recognized the gp33-41 CD8 + epitope from LCMV into naive mice. (acir.org)
Using multidimensional scaling analysis to cluster cells based on features of T cell exhaustion over time revealed that early (day 5) TP cells in chronic infection resembled established signatures for precursors of exhausted (day 21) T cells, while early TE cells from mice with chronic infection resembled the polyfunctional effector cells that were prominent in acute infection. (acir.org)
showed that P14 T cells lacking BACH2 failed to generate TP cell populations in mice with chronic LCMV infection, while overexpression of BACH2 enforced TP cell generation. (acir.org)
Mice were subsequently challenged with tumor cells, and the tumor protection was monitored. (bmj.com)
0.3% of the total circulating CD8 T cell population fully protects mice against lethal tumor challenge. (bmj.com)

Compared to healthy controls (n=24), DLBCL patients (n=33) showed significant lymphopenia, due to low CD3 + CD4 + T helper and CD3 - CD56 + NK cell counts, while cytotoxic CD3 + CD8 + T cell counts were similar. (frontiersin.org)
In vitro , CD3 + CD8 + CD27 - CD28 - compared to CD3 + CD8 + CD27 + CD28 + CART cells displayed similar CD19 + target cell-specific cytotoxicity, but were hypoproliferative and produced less cytotoxic cytokines (IFN-γ and TNF-α). (frontiersin.org)

However, many patients fail to respond to these therapies, and metabolic barriers imposed on T cells by the TME may contribute. (elifesciences.org)

However, although these new therapeutic strategies, which are designed to limit immune escape of cancer cells, have been used or tested successfully in many different cancers, a large proportion of patients have been described to resist and not respond to these new treatments. (oaepublish.com)
Clinical activity of TIL therapy has also been reported in other cancer types, including human papillomavirus-associated cancers, cholangiocarcinoma, non-small-cell lung cancer (NSCLC), and triple-negative breast cancer (TNBC). (biomedcentral.com)
However, except for virus-induced cancers, tumor antigens are mostly self or near-self protein epitopes that are often poorly immunogenic and submitted to central and peripheral tolerance. (biomedcentral.com)

Glioblastoma (GB) is the most frequent malignant primary brain tumor in adults, without any curative treatment options available at present. (frontiersin.org)
The importance of immune surveillance in eradicating malignant cells is well demonstrated, and several observations have motivated the development of therapeutic cancer vaccines. (biomedcentral.com)

Further growth of cancer cells selected during the Equilibrium phase may then lead to the acquisition of aggressive phenotypes and resistance to immune system elimination inducing clinical lesions. (oaepublish.com)
Blood cell and serum markers, along with clinical data of DLBCL patients who were scheduled for CART cell therapy were evaluated to search for biomarkers predicting CART cell responsiveness. (frontiersin.org)
In clinical practice, a key challenge for generating TIL products is the accessibility, quantity, and quality of tumor tissue in the era of neo-adjuvant therapy. (biomedcentral.com)
However, the clinical application of tumor-infiltrating γδ T cells has certain limitations. (explorationpub.com)

While these cells show some features of exhaustion, they maintain high proliferative potential and are able to both self-renew and replenish populations of exhausted effector T cells that mediate control in chronic viral infections and tumors. (acir.org)
The infused T cells traffic to tumors and can mediate their destruction. (biopharmconsortium.com)

Background Adoptive T cell transfer (ACT) therapy improves outcomes in patients with advanced malignancies, yet many individuals relapse due to the infusion of T cells with poor function or persistence. (bmj.com)
Despite this heterogeneous response, blood pre-infusion biomarkers predicting responsiveness to CART cell therapy are currently understudied. (frontiersin.org)
Low frequency of differentiated CD3 + CD27 - CD28 - T cells at leukapheresis represents a novel pre-infusion blood biomarker predicting a favorable response to CART cell treatment in r/r DLBCL patients. (frontiersin.org)

Besides, the effects of different T cell functional modulators and cytokines on TIL manufacture have also been examined. (biomedcentral.com)

One is the ability to administer large numbers of highly selected cells with high avidity for tumor antigens that can recognize shared and patient-specific mutated (neo) antigens. (biomedcentral.com)

Antibody-mediated depletion experiments further demonstrate that in this context, CTLs rather than NK cells are essential for the enhanced tumor inhibition. (biomedcentral.com)
These cells may be a key factor ultimately mediating the deviation of the antagonistic response between tumor inhibition and tumor promotion. (explorationpub.com)

Conclusions This study highlight the effectiveness of CMV-based vaccine vectors, and shows that demarcated thresholds of vaccine-specific T cells could be defined that correlate to tumor protection. (bmj.com)

Additionally, induced co -expression of luciferase, EGFP, and the melanosomal antigen gp100 facilitates studies on the underlying immunological mechanisms. (unav.edu)

Therefore, the ability to modify cells and manipulate their functions according to intended therapeutic designs has been the central scientific interest in the field of biomedical research. (biomedcentral.com)
Cell surface engineering to provide new characteristics and functions to cells has drawn continuous interest from researchers in biomedical science as cell therapy has emerged as a prominent therapeutic strategy equivalent and complementary to the conventional therapeutic approaches. (biomedcentral.com)

this was found to be the direct result of higher viral loads, and thus higher antigen burden in the chronic infection model. (acir.org)

The past decade has seen the discovery and development of novel treatments that harness the patient's immune system and prevent immune escape due to increased understanding of the tumor immune environment. (biomedcentral.com)
TIL therapy is a type of adoptive cellular therapy leveraging the patient's own immune system to treat tumors. (biomedcentral.com)
Lymphodepletion enhances adoptive T cell transfer (ACT) therapy by activating the innate immune system via microbes released from the radiation-injured gut. (biomedcentral.com)

In ACT, a physician/researcher extracts a patient's antigen-specific immune cells, which are usually found in tumor tissue. (biopharmconsortium.com)

So, immune escape has now been included as one of the new hallmarks of cancer development described in the revised version of Hanahan and Weinberg [ 5 ] in 2011, together with resistance to cell death, replicative immortality or induced angiogenesis, for example. (oaepublish.com)

Here we report that while exogenous administration of LPS was able to enhance adoptively transferred CD8 + T cells' tumor destruction, LPS treatment alone did not replace individual components of the tripartite ACT regimen, or obviate TBI. (biomedcentral.com)

Ly6G is expressed differentially during development by cells in the myeloid lineage including monocytes, macrophages, granulocytes, and neutrophils. (bioxcell.com)

Multiparametric flow cytometry and TCR sequencing studies showed that more than 30% of naïve T cells primed by antigen directly differentiate into TSCM cells. (wikipedia.org)

During the Elimination phase, some newly transformed cells can be quickly eliminated by immune effector cells, such as natural killers (NKs), but this phase can also favor the development of heterogeneous tumor cancer cells resulting in the selection of new variants resistant to immune edition. (oaepublish.com)

Advanced non-small cell lung cancer (NSCLC) is the most common type of lung cancer with poor prognosis. (thno.org)
Non-small cell lung cancer (NSCLC), the most common subtype, comprised approximately 85% of the newly diagnosed lung cancer cases [ 2 ]. (thno.org)
Combination of IL-2/15/21 can enhance TIL expansion in lung and colorectal cancer and promote CD8+ T cell percentage as well as TCR clone diversity compared to IL-2 alone [ 13 ]. (biomedcentral.com)

In past studies, researchers have identified a subset of T cells that serve as precursors to exhausted T cells. (acir.org)

Next, the researchers compared how TP and TE cells acquired features of exhaustion and found that both subsets upregulated PD-1 and TOX within 3 days of both chronic and acute infection. (acir.org)
When the researchers compared exhausted TP and TE cells from chronic infections against corresponding memory cells that developed after acute infection, they were able to identify a core exhaustion signature of 281 genes that included Pdcd1 , Lag3 , and Tox . (acir.org)
This shows that in the setting of chronic infection, TP cells acquire an exhaustion signature early on. (acir.org)
found that in chronic infection, exhaustion-related genes like Tox were highly accessible in early TP cells, mature TP cells, and mature TE cells. (acir.org)

After primary antigen exposure and elimination, antigen-specific TSCM preferentially survive among memory T cells and stably persist for a long term throughout the human lifespan. (wikipedia.org)

Many innovative methods have been developed with genetic modification of cells being the most advanced cell surface engineering technique. (biomedcentral.com)

The TME, however, can be metabolically hostile due to insufficient vascular exchange and cancer cell metabolism that leads to hypoxia, depletion of nutrients, and accumulation of waste products. (elifesciences.org)

A T memory stem cell (TSCM) is a type of long-lived memory T cell with the ability to reconstitute the full diversity of memory and effector T cell subpopulations as well as to maintain their own pool through self-renewal. (wikipedia.org)

Additionally, these cells show highly flexible and dynamic plasticity and are extremely easily polarized into regulatory phenotypes. (explorationpub.com)

In this study, we comprehensively screened HLA-A2 restricted MAGE-A3 tumor epitopes and characterized the corresponding TCRs using in vitro artificial antigen presentation cells (APC) system, single-cell transcriptome and TCR V(D)J sequencing, and machine-learning. (thno.org)
We identified the HLA-A2 restricted T cell epitopes from MAGE-A3 that could effectively induce the activation and cytotoxicity of CD8+ T cells using artificial APC in vitro . (thno.org)
A cohort of HLA-A2+ NSCLC donors demonstrated that the number of epitope specific CD8+ T cells increased in NSCLC than healthy controls when measured with tetramer derived from the candidate MAGE-A3 epitopes, especially epitope Mp4 (MAGE-A3: 160-169, LVFGIELMEV). (thno.org)

Anatomy27

Organisms15

Diseases48

Chemicals and Drugs80

Analytical, Diagnostic and Therapeutic Techniques and Equipment44

Phenomena and Processes47

Disciplines and Occupations1

Technology, Industry, Agriculture2

Information Science3

Health Care5

Immunotherapy27

Lymphocytes12

Chimeric1

Immunity9

Receptors4

Efficacy6

Microenvironment5

Vivo7

Solid tumors2

Melanoma4

Immunotherapies9

TILs2

Differentiation5

Potent5

TAAs2

Phenotype4

Regression2

Receptor4

Recognition4

Responses9

Mice9

Cytotoxic2

Therapies1

Cancers3

Malignant2

Clinical4

Mediate2

Infusion3

Cytokines1

Recognize1

Inhibition2

Conclusions1

Gp1001

Therapeutic2

Burden1

Immune system3

Tissue1

Weinberg1

Destruction1

Macrophages1

Differentiate1

Heterogeneous1

Lung3

Subset1

Exhaustion4

Elimination1

Methods1

Depletion1

Effector T cell1

Additionally1

Epitopes3