| First Author | Immisch L | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1119498 | PubMed ID | 36875127 |
| Mgi Jnum | J:343712 | Mgi Id | MGI:7443508 |
| Doi | 10.3389/fimmu.2023.1119498 | Citation | Immisch L, et al. (2023) Targeting the recurrent Rac1P29S neoepitope in melanoma with heterologous high-affinity T cell receptors. Front Immunol 14:1119498 |
| abstractText | Recurrent neoepitopes are cancer-specific antigens common among groups of patients and therefore ideal targets for adoptive T cell therapy. The neoepitope FSGEYIPTV carries the Rac1P29S amino acid change caused by a c.85C>T missense mutation, which is the third most common hotspot mutation in melanoma. Here, we isolated and characterized TCRs to target this HLA-A*02:01-binding neoepitope by adoptive T cell therapy. Peptide immunization elicited immune responses in transgenic mice expressing a diverse human TCR repertoire restricted to HLA-A*02:01, which enabled isolation of high-affinity TCRs. TCR-transduced T cells induced cytotoxicity against Rac1P29S expressing melanoma cells and we observed regression of Rac1P29S expressing tumors in vivo after adoptive T cell therapy (ATT). Here we found that a TCR raised against a heterologous mutation with higher peptide-MHC affinity (Rac2P29L) more efficiently targeted the common melanoma mutation Rac1P29S. Overall, our study provides evidence for the therapeutic potential of Rac1P29S-specific TCR-transduced T cells and reveal a novel strategy by generating more efficient TCRs by heterologous peptides. |
