PIK3CA gain-of-function mutations are among the most common alterations in human solid cancers. Through the use of stimulation-induced functional T cell receptor (TCR) sequencing (SIFT-seq), a panel of TCRs that bind a mutant PI3Kα shared neoantigen was identified, including a potential clinical candidate that engages cancer cells via a distinctive CDR3β loop.
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References
Priestley, P. et al. Pan-cancer whole-genome analyses of metastatic solid tumours. Nature 575, 210–216 (2019). This paper reports on the mutational landscape of more than 2,000 metastatic solid cancers.
Andre, F. et al. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N. Engl. J. Med. 380, 1929–1940 (2019). This paper reports on an FDA-registration-enabling clinical trial of apelisib for the treatment of cancers with mutated PIK3CA.
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This is a summary of: Chandran, S. S. et al. Immunogenicity and therapeutic targeting of a public neoantigen derived from mutated PIK3CA. Nat. Med. https://doi.org/10.1038/s41591-022-01786-3 (2022).
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PIK3CA hotspot mutation generates a shared neoantigen targetable by TCR gene therapy. Nat Med 28, 907–908 (2022). https://doi.org/10.1038/s41591-022-01806-2
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DOI: https://doi.org/10.1038/s41591-022-01806-2
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