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The point of the spear: Targeting MAGE-A4
PHILADELPHIA & OXFORD, U.K.—April 1 saw Adaptimmune Therapeutics plc, which works heavily in the area of T cell therapy to treat cancer, present preclinical data at the annual AACR meeting from its next-generation SPEAR (Specific Peptide Enhanced Affinity Receptor) T cell targeting MAGE-A4. This cell, known as ADP-A2M4CD8, expresses the CD8α co-receptor alongside the engineered TCR that targets the melanoma-associated antigen A4 (MAGE-A4) protein.
Co-expression of CD8α is anticipated to broaden the immune response against solid tumors and increase antitumor activity by converting CD4+ helper cells into CD8+ killer or cytotoxic T cells. The preclinical data reportedly demonstrate that the addition of CD8α with the engineered TCR in vitro improved engagement and function in CD4+ T cells that may support clonal expansion of CD8+ T cells, differentiation into effector and memory T cells, as well as engage the wider immune system in antitumor responses.
“Our next-generation programs are designed to enhance our existing SPEAR T cells, to improve their ability to target and kill solid tumors. The preclinical data we presented at AACR indicate that adding CD8a to our ADP-A2M4 candidate may help broaden the antitumor immune response against additional tumor antigens,” said Rafael Amado, Adaptimmune’s president of R&D. “Further, the CD8α co-receptor may enhance the ability of CD4+ SPEAR T cells to kill cancer cells through the engineered TCR targeting MAGE-A4.”
Adaptimmune is a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapy products. The company is currently conducting clinical trials with SPEAR T cells targeting MAGE-A4, MAGE-A10 and AFP across multiple solid tumor indications.