Facts and Hopes for Neoantigen-Enriched TIL.

After decades of development, adoptive transfer of tumor-infiltrating lymphocytes (TIL) or TIL immunotherapy was approved by the U.S. FDA for patients with checkpoint-refractory metastatic melanoma in 2024. Application of the strategy to more common epithelial cancers has depended on the translation of key findings about tumor and T-cell interactions derived from studies of patients with melanoma. Central to that effort has been the identification of neoantigens and neoantigen-reactive TIL. Using laboratory techniques to guide the selection of TIL has mediated modest tumor regression, but new strategies to enrich TIL remain in development in the hopes of improving clinical efficacy in the treatment of solid tumors.