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PIK3CA hotspot mutation generates a shared neoantigen targetable by TCR gene therapy

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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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Fig. 1: Therapeutic TCRs that target a PI3Kα public neoantigen.

References

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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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