NOVEL APPROACHES FOR CANCER IMMUNOTHERAPY WITH RECOMBINANT ANTIBODIES MIMICKING T-CELL RECEPTOR SPECIFICITY


Yoram Reiter
Biology, Technion-Israel Institute of Technology, Haifa

Tumour and virus-infected cells are recognized by CD8+ cytotoxic T cells that, in response, are activated to eliminate these cells. In order to be activated, the clonotypic T-cell receptor (TCR) needs to encounter a specific peptide antigen presented by the membrane surface major histocompatibility complex (MHC) molecule. Cells that have undergone malignant transformation or viral infection present on their MHC class I molecules peptides derived from tumour-associated antigens or viral proteins. Therefore, disease-specific MHC/peptide complexes are desirable targets for immunotherapeutic approaches. One such approach transforms the unique fine specificity but low intrinsic affinity of TCRs to MHC/peptide complexes into high-affinity soluble antibody molecules endowed with a TCR-like specificity toward tumour or viral epitopes. These antibodies, termed TCR-like antibodies, are being developed as a new class of immunotherapeutics that can target tumour and virus-infected cells and mediate their specific killing. In addition to their therapeutic capabilities, TCR-like antibodies are being developed as diagnostic reagents for cancer and infectious diseases, and can serve as valuable research tools for studying MHC class I antigen presentation.








 




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