P21

Mechanism (as reported)

null

Key findings (each cites a source)

• A study reported developing CAR-T cells that target tumors using binders against oncogenic KRAS G12V peptide-MHC complexes, incorporating neoantigen binders into CAR-T cells, and demonstrating efficacy in xenograft models (metastatic lung, pancreatic, and renal cell cancer). [PMID 40480232]
• The same study reported enhancing in vivo efficacy and safety of the KRAS-targeted CAR-T approach via inducible IL-12 secretion and T cell receptor deletion. [PMID 40480232]
• Research integrating proteogenomics and other datasets reported prioritizing mutant KRAS peptides as promising public neoantigens by combining proteomic data with MHC binding prediction. [PMID 38917788]
• A study reported identifying two TCRs specific for a 9-mer KRAS-G12V mutant neoantigen presented by HLA-A*11:01 and observing cytokine secretion and cytotoxicity when TCR-T cells were co-cultured with tumor cells expressing the KRAS-G12V mutation. [PMID 37828002]
• That TCR study reported that specific recognition of the KRAS-G12V mutant depends on distinct peptide conformation relative to wildtype and the direct interaction with TCR residues. [PMID 37828002]
• A study reported that a covalent K-Ras(G12C)-mutant inhibitor can induce MHC class I presentation of haptenated peptide neoepitopes in KRAS G12C mutant cells and that haptenated MHC-I complexes can serve as tumor-specific neoantigens. [PMID 36099883]
• The same covalent-inhibitor study reported that an ARS1620-specific antibody-based bispecific T cell engager elicited cytotoxic T cell responses against KRAS G12C cells, including those resistant to direct KRAS G12C inhibition. [PMID 36099883]
• A study reported that Klotho-derived peptide 1 (KP1) inhibited cellular senescence and restored Klotho expression at the posttranscriptional level, with effects including reduced senescence markers p21, p16, and γ-H2AX in diseased kidneys. [PMID 38164143]
• A separate study reported that a recombinant walnut-derived peptide (rWDP) was associated with decreased p21 expression in the hippocampus and cortex in d-galactose-induced aging mice. [PMID 40864666]