anti-CALRmut/anti-CD3 bispecific antibody JNJ-88549968

A bispecific antibody directed against both the mutated form of calreticulin (CALRmut; mutCALR) and the T-cell surface antigen CD3, with potential immunostimulating and antineoplastic activities. Upon administration, anti-CALRmut/anti-CD3 bispecific antibody JNJ-88549968 targets and binds to both CALRmut expressed on CALR mutated CD34-positive hematopoietic stem cells (HSCs) and CD3 on T cells. This results in the cross-linking of CALRmut-expressing tumor cells and T cells, and induces a cytotoxic T-lymphocyte (CTL) response against CALRmut-expressing tumor cells. CALR mutations, either insertions or deletions in exon 9, result in a frameshift that causes the loss of the KDEL ER retention motif. CALR mutations drive a variety of myeloproliferative neoplasms (MPNs).