NEO-STIM advances personalized neoantigen-specific adoptive T cell therapy

Abstract

Abstract Neoantigen-based adoptive T cell therapies (ACTs) represent a promising avenue in cancer immunotherapy due to their exquisite tumor specificity. The first cell-based immunotherapy for a solid tumor, comprising tumor-infiltrating lymphocytes, recently received FDA approval. Building on this, we designed a distinct ACT approach, where T cell responses against personalized neoantigens are systematically generated from autologous peripheral blood. Here we report the establishment of NEO-STIM, an ex vivo induction process to prime and expand pre-existing memory and de novo CD8 + and CD4 + T cell responses, thereby highlighting critical parameters for generating potent neoantigen-specific T cell responses. The drug products comprise mutant-reactive, polyfunctional, and cytotoxic CD8 + and CD4 + T cells, able to recognize autologous tumor material. Following infusion, T cell responses are detected in tumor and blood of a patient, and display activated/exhausted and cytotoxic phenotypes. A first-in-human clinical trial (NCT04625205) recently further validated proof-of-concept, supporting continued development of this ACT approach.