Mutant calreticulin-derived neoantigen peptide (CALR-mut neoantigen)

Mutant calreticulin (CALR) neoantigen peptides are novel protein sequences generated by frameshift mutations in exon 9 of the CALR gene, which are characteristic of myeloproliferative neoplasms (MPNs) such as essential thrombocythemia and primary myelofibrosis (Holmström et al., 2018; Schischlik et al., 2019). These mutations result in a common, highly immunogenic C-terminal tail that is absent in wild-type CALR and normal tissues, making it an ideal tumor-specific target (Schischlik et al., 2019; Boiocchi et al., 2016). Therapeutic strategies focus on leveraging this neoantigen through peptide-based vaccines or adoptive T-cell therapies to stimulate a robust cytotoxic T-lymphocyte response against the malignant clone (Holmström et al., 2018; ClinicalTrials.gov NCT03571321). Because the mutant C-terminus is shared across different patients with CALR mutations, it represents a public neoantigen, facilitating the development of standardized immunotherapies (Holmström et al., 2018; Schischlik et al., 2019). Clinical investigations are currently exploring the safety and efficacy of these approaches in patients with MPNs to achieve molecular remission and prevent disease progression (ClinicalTrials.gov NCT03571321). The specificity of these neoantigens minimizes the risk of off-target toxicity against healthy cells expressing wild-type CALR (Holmström et al., 2018).

Other names

CALR mutant neoantigenMutant CALR C-terminal peptideCALR exon 9 mutation-derived peptideCALR-mutated neoepitopeCALR-mutant C-terminus

Stimulation of a specific immune response by presenting mutant CALR-derived peptides on MHC molecules to activate cytotoxic T-lymphocytes (CTLs) and helper T-cells against malignant cells.