Mutant calreticulin neoantigen-MHC complex (CALR-mut neoantigen-MHC)

The mutant calreticulin (CALR) neoantigen-MHC complex is a highly specific therapeutic target found in patients with myeloproliferative neoplasms (MPNs), such as essential thrombocythemia and primary myelofibrosis. These diseases are frequently driven by frameshift mutations in exon 9 of the CALR gene, which result in a novel, shared C-terminal amino acid sequence that is entirely absent in wild-type cells. This mutant C-terminus acts as a 'public' neoantigen because the same novel sequence is generated across different patients with these mutations. The neoantigen is processed by the cellular proteasome and presented on the cell surface by Major Histocompatibility Complex (MHC) Class I and Class II molecules. Because this complex is unique to the malignant clone, it provides an ideal target for immunotherapy, allowing for the selective elimination of cancer cells while sparing healthy tissues. Current therapeutic strategies under investigation include peptide-based vaccines designed to stimulate endogenous T-cell responses and adoptive cell therapies using T-cell receptors (TCRs) engineered to recognize the CALR-mut peptide-MHC complex. Clinical studies have demonstrated that patients often harbor spontaneous T-cell responses against this neoantigen, suggesting that therapeutic amplification of this response could be clinically effective. The success of these therapies is often dependent on the patient's specific HLA (Human Leukocyte Antigen) type, which determines the efficiency of neoantigen presentation.

Other names

Mutated calreticulin neoantigenCALR exon 9 mutation neoantigenCALR-mut peptide-HLA complexMutant CALR C-terminus neoantigenCALR frameshift neoantigen

Induction of T-cell mediated cytotoxicity against cells presenting the mutant calreticulin peptide on MHC molecules, leading to the selective destruction of malignant hematopoietic cells.