With the development of molecular cloning technology and the deep understanding of antibody engineering, there are diverse bispecific antibody formats from which to choose to pursue the optimal biological activity and clinical purpose. The single-chain-based bispecific antibodies usually bridge tumor cells with immune cells and form an immunological synapse because of their relatively small size. Bispecific antibodies in the IgG format include asymmetric bispecific antibodies and homodimerized bispecific antibodies, all of which have an extended blood half-life and their own crystalline fragment (Fc)-mediated functions. Besides retargeting effector cells to the site of cancer, new applications were established for bispecific antibodies. Bispecific antibodies that can simultaneously bind to cell surface antigens and payloads are a very ideal delivery system for therapeutic use. Bispecific antibodies that can inhibit two correlated signaling molecules at the same time can be developed to overcome inherent
A trifunctional antibody is a monoclonal antibody with binding sites for two different antigens, typically CD3 and a tumor antigen, making it a type of bispecific monoclonal antibody. In addition, its intact Fc-part can bind to an Fc receptor on accessory cells like conventional monospecific antibodies. The net effect is that this type of drug links T cells (via CD3) and monocytes/macrophages, natural killer cells, dendritic cells or other Fc receptor expressing cells to the tumor cells, leading to their destruction. At an equivalent dose a trifunctional antibody is more potent (more than 1,000-fold) in eliminating tumor cells than conventional antibodies. These drugs evoke the removal of tumor cells by means of (i) antibody-dependent cell-mediated cytoxicity, a process also described for conventional antibodies and more importantly by (ii) polyclonal cytotoxic T cell responses with emphasis on CD8 T cells. These trifunctional antibodies also elicit individual anti-tumor immune responses in ...
TRION Pharma Release: Trifunctional Antibody Catumaxomab Triggers Vaccination Effect Against Cancer - read this article along with other careers information, tips and advice on BioSpace
Bispecific antibodies (bsAbs) participating T cells are rising as a probable immunotherapeutic tool for the treatment of hematologic malignancies. co-stimulus buy AescinIIB via the Compact disc137-Compact disc137 ligand axis through Compact disc137L reflection on MSCs. This research demonstrates that MSCs possess the potential to end up being utilized buy AescinIIB as mobile creation devices for bsAb-based growth immunotherapy in the potential. Launch T-cell getting bispecific antibodies (bsAbs) are a appealing device for cancers treatment. This course of antibodies creates a transient synapse between Testosterone levels cells and cancers cells by presenting to a surface area antigen on cancers cells with one limb and concurrently enrolling Testosterone levels cells via the Compact disc3 domains, which is normally the indication sending part of the T-cell receptor complicated.1 The polarization of the T-cell complicated network marketing leads to an activation of bsAb buy AescinIIB recruited T ...
Oncolytic viruses exploit the cancer cell phenotype to complete their lytic life cycle, releasing progeny virus to infect nearby cells and repeat the process. We modified the oncolytic group B adenovirus EnAdenotucirev (EnAd) to express a bispecific single-chain antibody, secreted from infected tumour cells into the microenvironment. This bispecific T-cell engager (BiTE) binds to EpCAM on target cells and cross-links them to CD3 on T cells, leading to clustering and activation of both CD4 and CD8 T cells. BiTE transcription can be controlled by the virus major late promoter, limiting expression to cancer cells that are permissive for virus replication. This approach can potentiate the cytotoxicity of EnAd, and we demonstrate using primary pleural effusions and peritoneal malignant ascites that infection of cancer cells with the BiTE-expressing EnAd leads to activation of endogenous T cells to kill endogenous tumour cells despite the immunosuppressive environment. In this way, we have armed EnAd to
Objective. The objective of this study was to determine the properties of a single-chain bispecific antibody (scBsAb) against human ovarian carcinoma and to develop this agent for potential use in human ovarian cancer.. Methods. ELISA and FACS were performed to determine the antigen-binding properties of the scBsAb. Its abilities to retarget the preactivated human peripheral blood mononuclear cells (PBMCs) to human ovarian carcinoma cell line SKOV3 cells and mediate their lysis in vitro were performed by a colorimetric MTT-based assay. Nude mice bearing human SKOV3 tumor xenografts were used to study the distribution and imaging of the scBsAb. Its pharmacokinetics in vivo was also studied in naive BALB/c mice.. Results. The scBsAb showed nearly identical ligand binding properties at each site relative to the individual monovalent single-chain antibody prototype molecules and could bridge SKOV3 and human T cell line Jurkat, which expresses CD3 antigens on the surface of cells together. It can ...
Outcomes of acute lymphoblastic leukemia (ALL) in older adults treated with chemotherapy are poor. The CD19/CD3 bispecific T-cell engager (BiTE) antibody blinatumomab is approved for refractory, relapsed or minimal/measurable residual disease (MRD)-positive B-cell ALL, but there is little experience in the upfront setting, including in older patients. We retrospectively analyzed outcomes of blinatumomab monotherapy in five newly diagnosed Philadelphia chromosome-negative B-cell ALL patients over 70 years. Three had cytokine release syndrome, treated with dexamethasone and/or tocilizumab, and four patients had neurotoxicity, treated with dexamethasone, without blinatumomab interruption. All five achieved complete remission (CR) after cycle one, three with undetectable MRD. All five were alive at 8 to 15 months. Three remained in MRD-negative CR. Two relapsed after cycle 3, one with extramedullary disease. In our small cohort of patients over 70 years, blinatumomab was safe initial therapy and ...
Therapeutic monoclonal antibodies [mAbs] have become molecules of choice to treat autoimmune disorders, inflammatory diseases and cancer. Moreover, bispecific/multispecific antibodies that target more than one antigen or epitope on a target cell or recruit effector cells [T cell, natural killer (NK) cell or Macrophage cell] towards target cells have shown great potential to maximize the benefits of antibody therapy. In the past decade, many novel concepts to generate bispecific and multispecific antibodies have evolved successfully into a range of formats from full bispecific immunoglobulin gammas [IgGs] to antibody fragments. Impressively, antibody fragments such as bispecific T-cell engager [BiTE], bispecific killer cell engager [BiKE], trispecific killer cell engager [TriKE], tandem diabody [Tandab] and dual-affinity-retargeting [DART] are showing exciting results in terms of recruiting and activating self-immune effector cells to target and lyse tumor cells. Promisingly, Fc antigen binding fragment
Schematic computer artwork of the monoclonal antibody Blinatumomab, a bi-specific T-cell engager (BiTE). Blinatumomab (trade name) specifically targets the CD19 antigen present on B cells. Blinatumomab enables a patients T cells to recognize malignant B cells. A molecule of blinatumomab combines two binding sites: a CD3 site for T cells and a CD19 site for the target B cells. CD3 is part of the T cell receptor. The drug works by linking these two cell types and activating the T cell to exert cytotoxic activity on the target cell.Blinatumomab is used as a second-line treatment against acute lymphoblastic leukemia. The background is depicting a cancer cell. - Stock Image C029/1340
Schematic computer artwork of the monoclonal antibody Blinatumomab, a bi-specific T-cell engager (BiTE). Blinatumomab (trade name) specifically targets the CD19 antigen present on B cells. Blinatumomab enables a patients T cells to recognize malignant B cells. A molecule of blinatumomab combines two binding sites: a CD3 site for T cells and a CD19 site for the target B cells. CD3 is part of the T cell receptor. The drug works by linking these two cell types and activating the T cell to exert cytotoxic activity on the target cell.Blinatumomab is used as a second-line treatment against acute lymphoblastic leukemia. - Stock Image C029/1339
1. Tran E, Robbins PF, Lu YC, Prickett TD, Gartner JJ, Jia L. et al. T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer. N Engl J Med. 2016;375:2255-62 2. Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discov Today. 2015;20:838-47 3. Topp MS, Gökbuget N, Stein AS, Zugmaier G, OBrien S, Bargou RC. et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. The Lancet Oncology. 2015;16:57-66 4. Goebeler ME, Bargou R. Blinatumomab: a CD19/CD3 bispecific T cell engager (BiTE) with unique anti-tumor efficacy. Leuk Lymphoma. 2016;57:1021-32 5. Klinger M, Benjamin J, Kischel R, Stienen S, Zugmaier G. Harnessing T cells to fight cancer with BiTE® antibody constructs-past developments and future directions. Immunological reviews. 2016;270:193-208 6. Stieglmaier J, Benjamin J, Nagorsen D. Utilizing the BiTE (bispecific T-cell engager) platform for immunotherapy of cancer. ...
New York, USA - August 26, 2019 - As a professional provider occupied in the antibody field for over 10 years, Creative Biolabs is committed to offering highly efficient bispecific antibodies (BsAbs) for industrial and scientific clients all round the world for the BsAbs applications in Oncology, Immunology, Diagnostics, Gene Therapy, Hematology, Ophthalmology, and Osteology.. As engineered macromolecules with two or more distinct binding specificities within one molecule, bispecific antibodies are mostly known for its application in cancer treatment by interfering with signaling pathways, redirecting cytotoxic immune cells, or delivering radioactive therapeutics, most of which act through T cell recruitment and NK cell recruitment, designed to bind tumor-associated antigens and CD3 or CD16/CD56. As an experienced antibody expert, Creative Biolabs is capable of offering BiTE, Triomab, DART, TandAb, and Tandem scFv-Fc BsAb in oncology to block a signaling pathway and its backup pathway, or one ...
Bispecific antibodies, which simultaneously recognize two different antigens, hold great therapeutic potential, but their broad application has been hindered by difficulties in developing stable antibody platforms, favorable pharmacokinetic properties and feasible large-scale manufacturing protocols. In this study, researchers from Genentech Inc. have taken a step in overcoming these problems, improving upon a previously used small-scale strategy, known as "knobs-into-holes," that employed sterically complementary mutations in the antibody heavy chain CH3 domain to promote heavy chain heterodimerization with a single common light chain to prevent heavy chain/light chain mispairing. The researchers adapted this technology into a two-part strategy that consists first of small-scale generation of bispecific antibodies lacking a common light chain and hinge disulfides to facilitate proof-of-concept studies, followed by the identification of a common light chain-bispecific antibody for large-scale ...
Get access to 25 years of experience in bispecific antibody development. 3 therapeutic antibodies on the market, 30+ in preclinical and clinical phases including bispecific antibodies.
[127 Pages Report] Check for Discount on Global Bispecific Antibody Sales Market Report 2016 report by QYResearch Group. Notes: Sales, means the sales volume of Bispecific Antibody Revenue,...
... Global Bispecific Antibody Market Opportunity, Drug Sales &
Kinase inhibitors such as ibrutinib have advanced treatment of chronic lymphocytic leukemia (CLL). However, there remains a need for adjunct treatments capable of deepening response or overcoming resistance to kinase inhibitors. CD19/CD3 bispecific antibodies (bsAbs) recruit endogenous T cells to form cytolytic synapses with CD19+ tumor cells. Blinatumomab, a CD19/CD3 bsAb designed in the 54 kDa BiTE format, is FDA approved for the treatment of some forms of acute lymphoblastic leukemia, and has potential for use in other B-cell malignancies. However, due to its short half-life of 2.1 hours, blinatumomab requires continuous intravenous dosing for efficacy. We have developed a novel CD19/CD3 bsAb in the 100 kDa single chain-Fv Fc format (19/3-scFv-Fc). With a half-life of approximately 7 days, 19/3-scFv-Fc may be suitable for weekly dosing, providing a significant logistical advantage. Here we investigated the potential use of 19/3-scFv-Fc for treatment of CLL. We first cultured peripheral blood ...
Tumor vaccines have to provide several signals for T cell activation. Among them, signal 1 (through TCR/CD3) and signal 2 (through CD28) are the most important. We herein describe a procedure to introduce anti-CD3 and anti-CD28 signals into any tumor cell which is susceptible to infection by Newcastle disease virus (NDV). We developed the ATV-NDV tumor vaccine which consists of patient-derived tumor cells (ATV) modified through infection by NDV. We tested for further improvement of vaccine efficiency the addition of two bispecific single-chain antibodies. They bind with one arm to the viral hemagglutinin-neuraminidase (HN) or fusion (F) protein of NDV expressed at the surface of the vaccine cells while the second arm is directed either against CD3 or CD28 of T cells. The aim of this study was to optimize the coupling of these new reagents to the tumor vaccine. When anti-CD3 and anti-CD28 molecules bind to the same anchoring viral molecule (e.g. HN), competition for binding could occur under ...
Persistence or recurrence of minimal residual disease (MRD) after chemotherapy results in clinical relapse in patients with acute lymphoblastic leukemia (ALL). In a phase 2 trial of B-lineage ALL patients with persistent or relapsed MRD, a T cell-engaging bispecific Ab construct induced an 80% MRD response rate. In the present study, we show that after a median follow-up of 33 months, the hematologic relapse-free survival of the entire evaluable study cohort of 20 patients was 61% (Kaplan-Meier estimate). The hema-tologic relapse-free survival rate of a subgroup of 9 patients who received allogeneic hematopoietic stem cell transplantation after blinatumomab treatment was 65% (Kaplan-Meier estimate). Of the subgroup of 6 Philadelphia chromosome-negative MRD responders with no further therapy after blinatumomab, 4 are in ongoing hematologic and molecular remission. We conclude that blinatumomab can induce long-lasting complete remission in B-lineage ALL patients with persistent or recurrent MRD. The
Zymeworks Doses First Patient in Phase 1 Trial of ZW25, a Novel Bi-Specific Antibody. Vancouver, BC, September 26, 2016--Zymeworks Inc., a biopharmaceutical company discovering and developing innovative multi-functional protein-based therapeutics, including bi-specific antibodies and drug conjugates for the treatment of cancer, announced today that the first patient was dosed in a Phase 1 clinical trial of ZW25 for treatment of HER2-expressing tumors.
The HER2 protooncogene encodes a 185-kD transmembrane phosphoglycoproteins, human epidermal growth factor receptor 2 (p185HER2), whose amplified expression on the cell surface can lead to malignant transformation. Overexpression of HER2/p185HER2 is strongly correlated with progression of human ovarian and breast carcinomas. Recent studies have shown that human T cells can be targeted with bispecific antibody to react against human tumor cells in vitro. We have developed a bispecific F(ab)2 antibody molecule consisting of a humanized arm with a specificity to p185HER2 linked to another arm derived from a murine anti-CD3 monoclonal antibody that we have cloned from UCHT1 hybridoma. The antigen-binding loops for the anti-CD3 were installed in the context of human variable region framework residues, thus forming a fully humanized BsF(ab)2 fragment. Additional variants were produced by replacement of amino acid residues located in light chain complementarity determining region 2 and heavy chain ...
polyneuropathy (1 grade 3), edema (1 grade 3), and pyrexia (1 grade 1). No anti-AMG 420 antibodies were detected at doses up to 800 μg/d. Six patients had a complete response, 1 each at 6.5, 100, and 200 µg/d, and 3 at 400 µg/d; responses were ongoing for the past 3 months. There also were 2 partial remissions, a partial response at 50 µg/d, and a very good partial response at 800 µg/d. All 3 patients treated at 400 µg/d had an MRD-negative complete response.. Clinical Implications: AMG 420 showed evidence of clinical activity in patients with relapsed or refractory multiple myeloma. No major toxicities were observed up to 400 µg/d, and that is the recommended dose for further investigation; dose-limiting toxicities at 800 µg/d were cytokine-release syndrome and peripheral polyneuropathy. (Also, refer to Abstract 592, which highlights the activity of AMG 701, another anti-BCMA bispecific T-cell engager.4) The bispecific T-cell engager technology has already shown efficacy in leukemia and ...
Clinical trial for childhood ALL , Efficacy and Safety of the BiTE Antibody Blinatumomab in Chinese Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)
Bispecific antibodies are a versatile class of targeted therapeutics designed to bind two different sites, which can be located on a single antigen or on two antigens. Although bispecific antibodies were conceptualized ~60 years ago, various challenges associated with protein engineering, stability and manufacturing delayed their wide-spread development. However, as of 2020, numerous validated platforms, i.e., those that have produced bispecific clinical candidates, are readily available (1). Using these platforms, the commercial clinical pipeline has grown to over 100 bispecific antibodies, ranging from tandem single-chain variable fragments (scFv) to full-length immunoglobulins with dual variable domains. Substantial growth in the pipeline has occurred only relatively recently, though. During the early 2010s, bispecific antibodies comprised less than 10% of the total number of antibody therapeutics entering clinical study per year, but this number rose to 25% by 2018. Reflecting the general ...
Hofmann M, Große-Hovest L, Bässler T, Pyz E, Bamberg ML, Aulwurm S, Bühring H-J, Schwartz K, Haen S, Schilbach K, Rammensee H-G, Salih HR and Jung G. Generation, selection and preclinical characterization of an Fc-optimized FLT3-antibody for the treatment of myeloid leukemia. Leukemia 26:1228-1237 (2012) Große-Hovest L, Müller S, Minoia R, Wolf E, Zakhartchenko V, Wenigerkind H, Lassnig C, Besenfelder U, Müller M, Lytton SD, Jung G, Brem G. Cloned transgenic farm animals produce a bispecific antibody for T cell mediated tumor cell killing. Proc Natl Acad Sci USA 101,6858-6863 (2004) Große-Hovest L, Hartlapp I, Marwan W, Brem G, Rammensee HG, Jung G. A recombinant bispecific single chain antibody induces targeted, supra-agonistic CD28 stimulation and tumor cell killing. Eur J Immunol 33, 1334-1340 (2003) Jung G, Große-Hovest L, Krammer PH, Rammensee HG. Target cell restricted triggering of the CD95 (APO-1/Fas) death receptor with bispecific antibody fragments. Cancer Res 61,1846-1848 ...
Blinatumomab is a cancer medicine that interferes with the growth and spread of cancer cells in the body. Blinatumomab is used to treat a certain type of acute lymphoblastic leukemia. This medicine is given after other cancer treatments have been tried without success. Blinatumomab was approved by the US Food and Drug...
Therapeutic antibodies have improved treatments of complex diseases such as cancer, viral infections and inflammatory diseases over the past three decades, due to their unique ability to specifically home in on surface proteins. A new generation of biologically engineered antibody drugs - bispecifics - combine the binding specificity of two antibodies in only one molecule. Roche has invented the CrossMAb technology to produce bispecific antibodies. Theres one cell line, and one production process; its just one molecule from the start.
cansSAR 3D Structure of 6BA5_P | POTENT AND SELECTIVE ANTITUMOR ACTIVITY OF A T-CELL ENGAGING BISPECIFIC ANTIBODY TARGETING A MEMBRANE-PROXIMAL EPITOPE OF ROR1 | 6BA5
Merus is using its Biclonics technology platform to generate differentiated therapeutics in the form of full length human IgG bispecific antibodies designed to recruit the immune system to eliminate cancer cells.
Bispecific antibodies are an alternative option for the treatment of certain types of cancer. They may also be used for more effective medical imaging.
A homogenous sample of identical bispecific antibody determinants, each determinant being composed of two L-H half-molecules linked by disulfide bonds, each L-H half-molecule being specific for a diff
Summary of Facts and Submissions. I. Appeal lies from the decision of the examining division to refuse the European patent application No. 04739378.0, entitled Pharmaceutical compositions comprising bispecific anti-CD3, anti-CD19 antibody constructs for the treatment of B-cell related disorders.. II. The examining division considered a main request and an auxiliary request and held that the subject-matter of claim 1 of both lacked inventive step.. III. With the statement of grounds of appeal the appellant submitted a main and two auxiliary requests.. IV. The board issued a communication pursuant to Article 15(1) RPBA, in which objections inter alia under Articles 56 and 84 EPC were raised by the board (Article 111(1) EPC).. V. In reply, the appellant submitted a letter dated 30 August 2016, accompanied by a new main request, and renumbered the previous main request as auxiliary request 3. The appellant later informed the board that he would not be represented at the oral proceedings.. VI. Oral ...
Bispecific T cell engager (BiTE®) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the bodys immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE® antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE® antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit www.biteantibodies.com.. About ...
Monoclonal antibodies (mAbs) are currently among the best remedies in the treatment of cancer disorders. Almost 12 anti-cancer therapeutic mAbs have been approved for clinical applications. Although mAbs have been found to target specific antigens, numerous impediments are emerged in cancer therapy by mAbs because of expression of a low level of the same antigens on the surface of normal cells. To exterminate tumor cells specifically, the current paper puts forward a novel strategy to target cancer cells more selectively by bispecific monoclonal antibody (bsmAb), which has an affinity against the tumor-specific antigens. Translocations in genes and chromosomes are known triggers for the development of human cancers. The mutations in gene profile could create novel tumor-specific proteins and receptors which could be detected using bsmAbs.
Next generation antibodies such as bispecific antibodies (bsAbs) and antibody-drug conjugates (ADC) have reached market maturity demonstrating strong therapeutic benefit for patients. (Diamantis & Banerji, 2016; Garber, 2014) However, targeting broadly expressed, tumor-associated rather than tumor-specific antigens by highly potent ADCs warrants early safety assessment due to the risk of severe on-target side effects in normal tissues. (Diamantis & Banerji, 2016) Recently, it was elegantly shown that tumor selectivity can be increased by bispecific engagement of two antigens and the application of affinity attenuated binding moieties within a bispecific format. (Mazor et al., 2015a; Mazor et al., 2015b; Robinson et al., 2008) In the presented study, simultaneous targeting of two clinically validated cancer antigens, c-MET and EGFR, was evaluated, as receptor cross-talk and signaling redundancies give rise to c-MET mediated resistance mechanism during anti-EGFR monotherapy. (Engelman et al., ...
Immatics is a clinical-stage biopharmaceutical company spearheading the development of advanced immunotherapies that are active against multiple cancer indications. Based in Tuebingen, Germany and Houston, Texas, the company has recognized that novel, better and safer targets are the key to developing future cancer immunotherapies. Immatics has revolutionized the identification and qualification of novel, proprietary and tumor-specific peptide antigens (TUMAPs) through its world-leading target and TCR discovery platform XPRESIDENT®. TUMAPs significantly expand the target space for immuno-oncology as they are not limited to surface proteins, which are the targets of classical antibodies or CAR-T therapies. Immatics believes that by using its TUMAP expertise it can unlock the significant potential of immuno-oncology drugs, such as adoptive cellular therapies, biologicals and vaccines to improve the treatment of a wide range of cancers.. Immatics pipeline includes several TCR-bispecifics and ...
IMCgp100, an anti-CD3 antibody fragment fused to a gp100-specific T cell receptor, yielded long-lasting responses in patients with advanced melanoma.
... Interim Phase 1 Data Presented at International Conference on Malign... Lymphomas Shows Dose Dependent Single Agent Activity ...BETHESDA Md. June 5 /- Micromet Inc. (Nasdaq...In the study relapsed incurable non-Hodgkins lymphoma (NHL) patient...,Micromets,BiTE,Antibody,Blinatumomab,(MT103/MEDI-538),Demonstrates,Durable,Responses,in,Patients,with,Relapsed,Non-Hodgkins,Lymphoma,medicine,advanced medical technology,medical laboratory technology,medical device technology,latest medical technology,Health
Adults with relapsed/refractory B-cell precursor ALL were randomized in a 2:1 ratio to receive blinatumomab or 1 of 4 pre-specified, investigator-chosen, SOC chemotherapy regimens. Randomization was stratified by age (, 35 years vs ≥ 35 years of age), prior salvage therapy (yes vs no), and prior allogeneic HSCT (yes vs no) as assessed at the time of consent.. The study consisted of up to a 3-week screening and pre-phase period, a treatment period consisting of induction with 2 cycles of either blinatumomab or SOC chemotherapy, a consolidation phase of up to 3 additional cycles of protocol-specified therapy, and a maintenance phase for up to an additional 12 months with protocol-specified therapy. A safety follow-up visit 30 days after the last dose of protocol-specified therapy and a long-term follow-up period were included. The long-term follow-up part of the study was discontinued prematurely based on a recommendation from the data monitoring committee (DMC) that the study be stopped for ...
2.1.2 If superiority of blinatumomab in the MRD positive group is shown, to compare the OS of blinatumomab in conjunction with chemotherapy to chemotherapy alone in patients with BCR-ABL-negative B cell precursor ALL who are MRD negative after induction and intensification chemotherapy, based on MFC assessment of residual blasts ...
Starting with a hybridoma cell line or antibody sequence, we can deliver from milligrams to grams of your custom bispecific antibodies. 100% royalty-free.
Antibody fragments, especially single-chain Fv fragments, have been established for the generation of immunoliposomes for targeted drug delivery in cancer therapy and other applications. Bispecific immunoliposomes should be useful for dual targeting addressing inter- and intratumoral heterogeneity of tumor antigen expression. Here, we established a protocol to generate dual-targeted immunoliposomes using genetically engineered scFv molecules recognizing two different tumor-associated antigens, EGFR and CEA (CEACAM5), applying a step-wise insertion of antibody-coupled micelles into preformed PEGylated liposomes. The dual-targeted immunoliposomes retained binding activity for both antigens and combined the selectivity of both antibodies within one liposome. Thus, these dual-targeted immunoliposomes should be suitable to deliver therapeutic payloads to tumor cells expressing EGFR or CEA, or both antigens.
The insulin-like growth factor 2 (IGF2) is an important target for cancer therapy. We have previously proposed an approach for fast and irreversible removal of IGF2 from the circulation by using monoclonal antibodies (mAbs) that bind to two or more non-overlapping epitopes on the same molecule. We provided initial evidence for the formation of oligomeric antibody-ligand complexes that can bind to cells expressing Fc gamma receptors (FcγRs) with high avidity using an antibody domain with relatively low affinity as one of the anti-IGF2 mAbs. Recently, we identified a mAb, m708.5, in a scFv format which binds to both IGF2 and IGF1 with very high (pM) affinity. Interestingly, and rather surprisingly, this mAb did not compete with our other high affinity mAb, m610.27, for binding to IGF2. Therefore, we generated a new bispecific mAb, m67, by combining m708.5 and m610.27. As expected m67 potently inhibited binding of IGF2 to cells expressing the IGF1R and its phosphorylation, and resulted in ...
Objective: Biologicals targeting epidermal growth factor (EGF) and interleukin 13 receptors not only react with overexpressed markers on cancer cells but also react with receptors on normal cells. Because we developed novel bispecific ligand-directed toxins synthesized by cloning EGF and interleukin 13 on the same molecule with toxin, our objective was to determine whether we could block normal receptors while still targeting receptors overexpressed on cancer cells, thereby decreasing toxicity while maintaining efficacy. Methods: A method, toxicity blocking (ToxBloc), was developed in which a bolus intraperitoneal dose of recombinant EGF13 (without toxin) was given to mice approximately 15 to 20 minutes before DTEGF13. Experiments were then performed to determine whether the maximal tolerated dose (MTD) was reduced and whether we were still able to eliminate progression of aggressive human, metastatic, pancreatic cancer induced by orthotopic injection (OT) in nude mice. Results: ToxBloc ...
The present invention utilizes two monoclonal antibodies, 679 and hMN14, and two point mutations of 679, (679-VH (I3Q) and 679-VK(C101S)), to produce antigen specific diabodies. In addition, a bispecific diabody is produced from hMN14 and h679, which is obtained by grafting the CDRs of 679 onto a framework of amino acid residues found in human antibodies. The murine monoclonal antibody designated 679 (an IgGl, K) binds with high affinity to molecules containing the moiety histamine-succinyl-glycyl (HSG) (Morel etal, Molecular Immunology, 22, 995-1000, 1990). The nucleotide sequence pertaining to the variable domains (VH and VK) of 679 has been determined (Qu et al., unpublished results). VK is one of two isotypes of the antibody light chains, Vu As depicted in Figure 1, the design of the gene construct (679-scFv-L5) for expressing a 679 diabody possesses the following features: 1) The carboxyl terminal end of VH is linked to the amino terminal end of VK by the peptide linker Gly-Gly-Gly-Gly-Ser ...
After a challenging period, bispecific antibodies (bsAbs) are making a comeback in hematology as they become a prominent drug class and a major threat to CARs. Historically, excitement around bsAbs peaked in 2012 following the Amgen (AMGN)/Micromet acquisition but gradually faded due to disappointing results for Amgens Blincyto and other bsAbs. Blincyto (a CD19xCD3 T…
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Covagen (a Cilag GmbH International company) is developing bi- and trispecific antibodies, FynomAbs®, for the treatment of inflammation and cancer. The company
SAN DIEGO--(BUSINESS WIRE)-- Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) today announced that it has entered into a commercial license and supply agreement with Amgen, granting rights to use Ligands Captisol technology in the formulation of AMG 330. Captisol is a patent protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. AMG 330 is an anti-CD33 x anti-CD3 (BiTE®) bispecific antibody construct. It is being investigated as a treatment for acute myeloid leukemia by Amgen. This license agreement replaces the prior research agreement which allowed Amgen to evaluate AMG 330 with Captisol in preclinical and early clinical studies. Under this new commercial license agreement, Amgen receives exclusive worldwide rights to combine Captisol with AMG 330 for use in humans for a wide variety of therapeutic indications. In addition to an upfront payment, Ligand is entitled to potential milestone payments, royalties and revenue from ...