The calreticulin (CALR) exon 9 mutations are promising targets for cancer immune therapy

The calreticulin ( CALR ) exon 9 mutations are found in ∼30% of patients with essential thrombocythemia and primary myelofibrosis. Recently, we reported spontaneous immune responses against the CALR mutations. Here, we describe that CALR-mutant ( CALR mut)-specific T cells are able to specifically recognize CALR mut cells. First, we established a T-cell culture specific for a CALR mut epitope. These specific T cells were able to recognize several epitopes in the CALR mut C terminus. Next, we established a CALR mut-specific CD4 + T-cell clone by limiting dilution. These CD4 + T cells recognized autologous CALR mut monocytes and hematopoietic stem cells, and T-cell recognition of target cells was dependent on the presence of CALR . Furthermore, we showed that the CALR mut response was human leukocyte antigen (HLA)-DR restricted. Finally, we demonstrated that the CALR mut-specific CD4 + T cells, despite their phenotype, were cytotoxic to autologous CALR mut cells, and that the cytotoxicity was mediated by degranulation of the T cells. In conclusion, the CALR exon 9 mutations are targets for specific T cells and thus are promising targets for cancer immune therapy such as peptide vaccination in patients harboring CALR exon 9 mutations.