T-cell receptor on CD4+ T lymphocytes specific for KRAS neoantigen–MHC-II complexes (KRAS-MHC-II TCR)

The T-cell receptor (TCR) on CD4+ T lymphocytes specific for KRAS neoantigen–MHC-II complexes is a specialized immune receptor engineered to recognize mutated KRAS proteins presented by Major Histocompatibility Complex class II (MHC-II) molecules (NIH, 2019). KRAS is a prominent oncogenic driver, with mutations such as G12D and G12V occurring frequently in pancreatic, colorectal, and lung cancers (ASCO, 2024). These mutations produce neoantigens that are absent in normal tissues, making them ideal targets for precision immunotherapy (Nature Communications, 2022). While traditional TCR-T therapies often focus on MHC class I-restricted CD8+ T cells, targeting MHC-II-restricted neoantigens engages CD4+ T cells, which provide critical helper functions, including the secretion of Th1 cytokines like interferon-gamma and the activation of other immune effectors (JCI Insight, 2025). This dual approach can enhance the durability and potency of the anti-tumor response and overcome the immunosuppressive tumor microenvironment (Frontiers in Immunology, 2025). Therapeutic development involves isolating these specific TCRs from patients or healthy donors and using them to create TCR-engineered T cells for adoptive cell transfer (NCI, 2022). Clinical trials, such as those evaluating NW-301V, have shown that these therapies can induce significant tumor regression in patients with advanced epithelial cancers harboring KRAS mutations (ESMO, 2025).

Other names

MHC-II-restricted KRAS-specific TCRCD4+ KRAS-specific TCRHLA-DR-restricted KRAS TCRHLA-DP-restricted KRAS TCRKRAS neoantigen-specific T-cell receptor

Engineered T cells expressing these TCRs recognize KRAS mutant peptides (e.g., G12D, G12V) presented by MHC-II molecules on tumor cells or antigen-presenting cells, triggering T-cell activation, Th1 cytokine release (IFN-gamma, TNF-alpha), and coordinated anti-tumor immune responses (NIH, 2019; JCI Insight, 2025).