KRAS mutation-specific T-cell receptor (KRAS TCR)

The T-cell receptor (TCR) recognizing KRAS–peptide–MHC complexes is a specialized immune receptor engineered to target cells expressing mutated KRAS proteins, which are hallmark drivers in pancreatic, colorectal, and lung adenocarcinomas (NIH, 2015; Cancer.gov, 2017). These mutations, such as G12D and G12V, result in the presentation of unique neoantigen peptides by Major Histocompatibility Complex (MHC) molecules, specifically certain HLA alleles like HLA-A*11:01 or HLA-C*08:02 (JCI Insight, 2025; Nature Communications, 2023). The TCR specifically binds to these complexes, allowing engineered T cells (TCR-T therapy) to distinguish between mutant and wild-type KRAS with high precision (Kactus Bio, 2025). Clinical-stage candidates such as AFNT-211, NT-112, and NW-301V are being evaluated for their ability to induce tumor regression in patients with advanced solid tumors (Cancer.gov, 2024; ESMO, 2025). The therapeutic process involves isolating a patient's T cells, transducing them with the specific TCR gene, and reinfusing them following lymphodepleting chemotherapy (Cancer.gov, 2024). While promising, these therapies face challenges including cytokine release syndrome (CRS) and potential off-target cross-reactivity with similar self-peptides like RAB7B (BMJ, 2025; ESMO, 2025). Efficacy is highly dependent on the precise match between the tumor's KRAS mutation and the patient's HLA genotype (JCI Insight, 2025).

Other names

KRAS-specific T-cell receptorKRAS mutation-reactive T-cell receptorKRAS-targeted TCRTCR recognizing KRAS neoantigensKRAS-specific TCR

Adoptive T-cell therapy (TCR-T) where engineered T cells express a TCR that specifically recognizes KRAS mutant peptides presented by MHC/HLA molecules, leading to targeted tumor cell lysis.