T-cell receptor recognizing mutant KRAS peptide-MHC complexes (KRAS-specific TCR)

The T-cell receptor (TCR) recognizing mutant KRAS peptide-MHC complexes is a specialized immune receptor utilized in adoptive cell therapy to target oncogenic driver mutations in solid tumors (kactusbio.com, 2025). KRAS is one of the most frequently mutated genes in human cancers, particularly in pancreatic, colorectal, and lung adenocarcinomas, where hotspot mutations such as G12D and G12V create unique neoantigens (nih.gov, 2024). These TCRs are engineered into a patient's T cells to enable the recognition of mutant KRAS peptides presented by specific Human Leukocyte Antigen (HLA) molecules on the surface of cancer cells (cancer.gov, 2017). Upon binding to the peptide-MHC complex, the TCR-engineered T cells (TCR-T) are activated to proliferate and release cytotoxic factors, such as granzymes and perforin, leading to the selective destruction of tumor cells (frontiersin.org, 2022). This therapeutic approach is highly specific to the tumor because the target neoantigens are not expressed in healthy tissues, although its use is restricted to patients with matching HLA genotypes (esmo.org, 2025). Clinical trials have demonstrated the potential for significant tumor regression in patients with advanced, treatment-resistant KRAS-mutant cancers (aacrjournals.org, 2024). Safety considerations for these therapies include cytokine release syndrome and potential off-target reactivity, though the latter is minimized by the neoantigen-specific nature of the TCR (clinicaltrials.gov, 2026). Ongoing research focuses on expanding the library of available TCRs to cover a broader range of KRAS mutations and HLA alleles to increase patient eligibility (tandfonline.com, 2021).

Other names

Mutant KRAS-specific T-cell receptorKRAS neoantigen-specific T-cell receptorKRAS-reactive T-cell receptorKRAS-TCR

Adoptive cell transfer of autologous T cells genetically engineered to express a specific T-cell receptor (TCR) that recognizes mutant KRAS peptides (e.g., G12D, G12V) presented by specific Human Leukocyte Antigen (HLA) molecules on tumor cells, leading to T-cell activation and tumor cell lysis.