Neoantigen-major histocompatibility complex (MHC) complex (NeoAg-MHC)

The Neoantigen-major histocompatibility complex (MHC) complex is a personalized therapeutic target formed by the presentation of tumor-specific mutated peptides on the cell surface [2, 4]. These complexes are recognized by the native T-cell receptors (TCRs) of Tumor-Infiltrating Lymphocytes (TILs), which are immune cells that have naturally migrated into the tumor microenvironment [2]. 'Young TILs' refer to a specific preparation of these lymphocytes that are expanded rapidly in vitro to preserve their proliferative capacity and effector function [3]. The interaction between the TCR and the pMHC complex triggers a cytotoxic response, leading to the secretion of pro-inflammatory cytokines and the direct lysis of the malignant cell [2]. This target is highly specific to the individual patient's tumor, as neoantigens arise from unique somatic mutations not present in healthy tissue [4]. Lifileucel (Amtagvi) is the first FDA-approved therapy that utilizes this mechanism to treat advanced melanoma [1]. Therapeutic efficacy depends on the diversity of the TIL population and the density of the pMHC complexes on the tumor surface [2, 3]. Challenges include the requirement for high-intensity lymphodepletion and high-dose interleukin-2 to support the transferred cells [1]. Sources: [1] FDA. (2024). FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma. [2] Rosenberg, S. A., & Restifo, N. P. (2015). Adoptive cell transfer as personalized immunotherapy for human cancer. Science. [3] Besser, M. J., et al. (2010). Clinical responses in metastatic melanoma patients treated with a 'young' TIL product. Clinical Cancer Research. [4] Schumacher, T. N., & Schreiber, R. D. (2015). Neoantigens in cancer immunotherapy. Science.

Other names

Neoantigen-HLA complexpMHC complexNeoepitope-HLA complexTumor-specific antigen-MHC complexPatient-specific tumor-associated antigens presented as peptide-MHC complexes recognized by native TCRs on Young TILs

Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) that recognize and bind to specific neoantigen-MHC complexes on tumor cells, leading to cytotoxic T-cell mediated lysis.