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A humanized anti-b7h3×4-1BB bispecific antibody exerts potent antitumour effects through the activation of innate and adaptive immunity.
Biochem Biophys Res Commun
January 2025
Department of Pharmacology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning Province, China. Electronic address:
Agonistic monoclonal antibodies targeting 4-1BB have shown much preclinical promise, but their clinical development has been limited by obvious toxicity or unremarkable efficacy. Here, we generated two humanized anti-B7H3 × 4-1BB bsAbs (HK056-001/002) by fusing an anti-4-1BB scFv to the C-terminus of an anti-B7H3 with an intact Fc fragment from human IgG1 or IgG4. The two bsAbs were able to stimulate the 4-1BB signaling pathway, which was strictly dependent on B7H3 expression.
View Article and Find Full Text PDFA Strategy for Simultaneous Engineering of Interspecies Cross-Reactivity, Thermostability, and Expression of a Bispecific 5T4 x CD3 DART Molecule for Treatment of Solid Tumors.
Antibodies (Basel)
January 2025
MacroGenics Inc., Rockville, MD 20850, USA.
Bispecific antibodies represent a promising class of biologics for cancer treatment. However, their dual specificity and complex structure pose challenges in the engineering process, often resulting in molecules with good functional but poor physicochemical properties. To overcome limitations in the properties of an anti-5T4 x anti-CD3 (α5T4 x αCD3) DART molecule, a phage-display method was developed, which succeeded in simultaneously engineering cross-reactivity to the cynomolgus 5T4 ortholog, improving thermostability and the elevating expression level.
View Article and Find Full Text PDFInjection site reaction to teclistamab in a patient with multiple myeloma.
JAAD Case Rep
February 2025
Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania.
Discovery of a common light chain bispecific antibody targeting PD-1 and PD-L1 by Hybridoma-to-Phage-to-Yeast (H2PtY) platform.
Antib Ther
January 2025
Biologics Innovation Institute, Shanghai Jemincare Pharmaceutical Co., Ltd., Lane 535, Huanqiao Road, Pudong New Area, Shanghai 201315, China.
Background: Therapeutic antibody drugs targeting the PD-1 pathway are generally characterized by relatively low response rates and susceptibility to drug resistance during clinical application. Therefore, there is an urgent need for alternative therapeutic strategies to increase the immune response rate. Bispecific antibodies co-targeting PD-1 and PD-L1 may have greater potential to improve the efficacy of the immune checkpoint pathway.
View Article and Find Full Text PDFEffective cancer immunotherapy combining mRNA-encoded bispecific antibodies that induce polyclonal T cell engagement and PD-L1-dependent 4-1BB costimulation.
Front Immunol
January 2025
Department of Antibody Engineering, Leadartis SL, Tres Cantos, Madrid, Spain.
Background: Immune checkpoint inhibitors have revolutionized cancer therapy, but many patients fail to respond or develop resistance, often due to reduced T cell activity. Costimulation via 4-1BB has emerged as a promising approach to enhance the effector function of antigen-primed T cells. Bispecific T cell-engaging (TCE) antibodies are an effective way to provide tumor-specific T cell receptor-mediated signaling to tumor-infiltrating lymphocytes.
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