Direct Selection Of A Human Antibody Fragment Directed Against The Mage a1 tcr t products, recognizing epitopes on a*02:01 and c*07:02 approved for clinical development. here we report discovery and lead selection of a mage a1 tcr rec ognizing an epitope on a*01:01 (~24% population frequency). methods we discovered tcrs specific for an a*01:01 restricted mage a1 derived epitope using tscan’s proprietary. The hla a2 restricted epitope mage a1 278 , known to be processed and presented by human cancer cells in the context of hla a2 (ref. 14), differs by six out of nine amino acids from its murine.
Direct Selection Of A Human Antibody Fragment Directed Against The By interrogating cancer patients who are responding to immune checkpoint blockade therapy, we successfully identified tcr and relevant antigens that drive positive clinical response. one suc. Fh magic tcr t is an autologous cd8 and cd4 t cell product transduced with a transgenic t cell receptor (tcr) targeting mage a1. mage a proteins are classified within the “testis restricted” cancer testis antigens and are broadly expressed in a wide range of malignancies, including urothelial carcinomas, triple negative breast cancers. Background melanoma associated antigen 1 (mage a1) is a cancer testis antigen with highly selective expression in testis (which is an immune privileged site) and in multiple high unmet medical need cancers. therefore, it represents an attractive target for t cell receptor (tcr) based therapies. tk 8001 is a mage a1 directed tcr with optimized affinity and specificity, derived from the hutcr. Indeed, although mage a3–specific t cell clones were isolated from the peripheral blood of a melanoma patient vaccinated with a recombinant canarypox virus encoding human leukocyte antigen (hla)–a*01–restricted mage a1 and a3 epitopes , these t cells showed low functional avidity . adoptive therapy with tcr gene–modified t cells could.
Direct Selection Of A Human Antibody Fragment Directed Against The Background melanoma associated antigen 1 (mage a1) is a cancer testis antigen with highly selective expression in testis (which is an immune privileged site) and in multiple high unmet medical need cancers. therefore, it represents an attractive target for t cell receptor (tcr) based therapies. tk 8001 is a mage a1 directed tcr with optimized affinity and specificity, derived from the hutcr. Indeed, although mage a3–specific t cell clones were isolated from the peripheral blood of a melanoma patient vaccinated with a recombinant canarypox virus encoding human leukocyte antigen (hla)–a*01–restricted mage a1 and a3 epitopes , these t cells showed low functional avidity . adoptive therapy with tcr gene–modified t cells could. Two of the top scoring peptides were the only 2 library antigens containing the known mage a3 epitope (figure 6 b). furthermore, the 2 corresponding 90 mers from the related mage a6 gene—that contain the same 9 mer hla a1 epitope apart from a single leucine to valine substitution—also enriched reproducibly (figure 6 c). the remaining 4. Finally, they applied t scan to understand the specificity of tumor reactive tcr in a human genome wide library using a tcr targeting hla a1 restricted epitope of tumor antigen mage a3. the top two enriched epitopes were confirmed as either known mage a3 epitopes or epitopes derived from the related protein mage a6.
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