inca033989

INCA033989 is a fully human immunoglobulin G1 (IgG1) monoclonal antibody that selectively targets the mutated form of calreticulin (mutCALR), a driver mutation found in certain myeloproliferative neoplasms (MPNs) such as myelofibrosis and essential thrombocythemia. By binding with high affinity to mutant CALR, INCA033989 antagonizes its oncogenic function, resulting in selective inhibition of JAK/STAT signaling only in CALR-mutated cells. This leads to reduced proliferation and survival of malignant cells while sparing normal hematopoietic cells. The drug acts by promoting endocytosis of the mutCALR/TPO-R complex, thereby suppressing downstream signaling pathways critical for disease progression. Preclinical studies have shown that INCA033989 can reduce mutant cell burden and preserve normal blood cell production, suggesting potential for disease modification without significant toxicity[1][2][5][7].

Other names

anti-mutant calreticulin monoclonal antibody inca033989