T-cell receptor recognizing HLA-presented SMC1A frameshift neoantigen (TCR-SMC1A-fs)

The T-cell receptor (TCR) recognizing HLA-presented SMC1A frameshift neoantigens is a specialized immune receptor found on CD4+ and CD8+ T-cells that mediates the recognition of tumor-specific mutations. Structural Maintenance of Chromosomes 1A (SMC1A) frequently undergoes frameshift mutations in cancers characterized by microsatellite instability (MSI), such as colorectal and gastric cancers, resulting in the production of novel, highly immunogenic C-terminal peptide sequences. These neoantigens are absent in healthy tissues, making the TCRs that recognize them ideal candidates for highly specific cancer immunotherapies. When these TCRs bind to the SMC1A frameshift peptide-HLA complex, they trigger T-cell activation, leading to the targeted destruction of malignant cells. Current therapeutic development focuses on identifying high-affinity TCR sequences for use in adoptive TCR-T cell therapies and designing vaccines to elicit these specific T-cell responses. Because the SMC1A frameshift is a recurrent 'hotspot' mutation in MSI-high tumors, these TCRs represent a promising 'off-the-shelf' target for personalized immunotherapy in a defined patient population.

Other names

SMC1A frameshift-specific T-cell receptorHLA-restricted SMC1A neoantigen-specific TCRSMC1A-fs-reactive TCRT-cell receptor recognizing SMC1A frameshift peptide-HLA complexes

The target is a T-cell receptor (TCR) that specifically binds to a neoantigen peptide derived from a frameshift mutation in the SMC1A gene, presented by Human Leukocyte Antigen (HLA) molecules. Therapeutic strategies involve either vaccinating patients to expand endogenous T-cells bearing these TCRs or engineering patient T-cells to express these specific TCRs (TCR-T therapy) to selectively recognize and kill tumor cells expressing the SMC1A frameshift mutation.