T cell receptor specific for mutated Mitogen-activated protein kinase 1 (ERK2-specific TCR)

The T cell receptor (TCR) specific for ERK2-epitopes is a specialized protein complex found on the surface of T cells that has been programmed to recognize mutated forms of the Extracellular signal-regulated kinase 2 (ERK2), also known as Mitogen-activated protein kinase 1 (MAPK1). These mutations, most notably the E222K substitution, function as neoantigens—proteins unique to cancer cells that are not found in normal tissues (Robbins et al., 2013, Nature Medicine). The TCR functions by binding to these mutated peptides when they are presented by specific Major Histocompatibility Complex (MHC) molecules, typically HLA-A*02:01, on the surface of tumor cells. This recognition event triggers T cell activation, leading to the secretion of perforins, granzymes, and cytokines like IFN-gamma to destroy the target cell (Tran et al., 2014, Science). In therapeutic contexts, these TCRs are often cloned and inserted into a patient's own T cells via viral vectors to create TCR-engineered T cell therapies (TCR-T). This approach is particularly promising for treating solid tumors such as melanoma and colorectal cancer, where ERK2 mutations can drive oncogenesis. By targeting these tumor-specific neoantigens, the TCR allows for highly selective immunotherapy with minimal impact on healthy cells. Clinical development focuses on identifying high-affinity TCR sequences and ensuring HLA compatibility for patient selection.

Other names

MAPK1-specific T cell receptorERK2-E222K specific TCRNeoantigen-specific T cell receptorERK2-epitope-specific TCRT cell receptor on ERK2-epitope-specific T cells

The TCR specifically binds to a mutated ERK2 peptide (such as the E222K neoantigen) presented by Major Histocompatibility Complex (MHC) Class I molecules, initiating a signaling cascade that results in the cytotoxic destruction of the tumor cell.