Mutant calreticulin neoantigen peptide-MHC-I complex (Mutant CALR neoantigen)

Mutant calreticulin (CALR) neoantigen peptides are novel protein sequences generated by frameshift mutations in exon 9 of the CALR gene, which occur in approximately 25-30% of patients with essential thrombocythemia and primary myelofibrosis (Nangalia et al., 2013; Klampfl et al., 2013). These mutations result in a shared, highly basic C-terminal tail that is entirely absent in wild-type CALR, making it a tumor-specific neoantigen. When these mutant peptides are processed and presented by Major Histocompatibility Complex class I (MHC-I) molecules on the surface of malignant cells, they can be recognized by CD8+ cytotoxic T cells (Holmström et al., 2018). This recognition triggers an immune response aimed at eliminating the neoplastic clones. Because the neoantigen is shared among many patients and is not expressed in healthy tissues, it serves as an ideal target for immunotherapies, including peptide-based vaccines and TCR-engineered T-cell therapies (Schischlik et al., 2019). Current research focuses on identifying the specific HLA alleles, such as HLA-A*03:01, that most effectively present these peptides to ensure broad clinical applicability and efficacy in treating myeloproliferative neoplasms.

Other names

CALR exon 9 mutation neoantigenMutant CALR-derived neoantigenCALR-mutant peptide-HLA complexMutant CALR C-terminusCALR-mutant neoepitope

Induction of CD8+ T-cell mediated cytotoxic immune response against malignant cells expressing the mutant calreticulin protein.