Mutant calreticulin–directed immunotherapies in myeloproliferative neoplasms
Key claim: Mutant calreticulin’s abnormal C-terminal tail is a promising immunotherapy target in MPNs, with antibody-based approaches leading and CAR-T and vaccine strategies in early clinical testing.
Abstract
An expert review published in Blood Neoplasia in 2026 discusses how mutations in calreticulin represent the second most common cancer-driving mutation in MPNs, and produce an abnormal C-terminal tail (a changed end section of the protein) that makes this mutation a promising target for immunotherapy. Using antibodies to target mutant CALR is the leading treatment approach, while vaccines directed against mutant CALR and chimeric antigen receptor (CAR) T-cells directed against mutant CALR are also being tested in early clinical trials.
Why this matters
Mutant calreticulin generates a tumor-specific C-terminal neoepitope shared across CALR-mutant MPN patients, making it one of the cleanest neoantigen targets in hematologic oncology. This review consolidates the three-modality landscape — antibodies (most advanced, e.g., INCA033989, JNJ-88549968), CAR-T, and peptide vaccines — providing a framework for tracking how mutation-selective immunotherapy is reshaping MPN treatment beyond JAK inhibition.