Multiple tumor-associated antigens presented on peptide-MHC complexes (TAA-pMHC)

Multiple tumor-associated antigens (TAAs) presented on peptide-major histocompatibility complexes (pMHC) represent a therapeutic target class focused on the HLA-restricted presentation of intracellular cancer proteins. These targets are generated when proteins overexpressed or mutated in tumor cells are processed into short peptides and displayed on the cell surface, allowing T-cells to identify malignant cells based on their internal proteome (Walter et al., 2012, Nature Medicine). By targeting a broad repertoire of these peptides simultaneously, therapies aim to address tumor heterogeneity and prevent the emergence of resistant clones that have lost a single antigen (Hilf et al., 2019, Nature). This approach is primarily utilized in the development of multi-peptide vaccines and adoptive T-cell therapies, which are designed to elicit a robust, poly-specific cytotoxic T-lymphocyte response. Drugs such as IMA901 and IMA950 are examples of this strategy, incorporating multiple tumor-associated peptides (TUMAPs) to maximize the breadth of the immune attack (Rampling et al., 2016, Clinical Cancer Research). The clinical utility of this target class is being explored across various solid tumors, including glioblastoma and renal cell carcinoma, where it offers a way to target non-surface proteins that are otherwise inaccessible to conventional antibodies.

Other names

Tumor-associated peptidesTUMAPsHLA-presented tumor antigensMulti-antigen peptide-HLA complexesCancer-specific peptide-MHC complexesMulti-peptide tumor-associated antigens

Stimulation of a poly-specific T-cell response where multiple distinct T-cell populations recognize different peptide-HLA complexes on the tumor surface, leading to synergistic cell lysis and reduced immune escape (Hilf et al., 2019, Nature).