Identification of an HLA-A1 restricted CTL epitope from Mcl-1

Spontaneous high-titered IgG antibody responses against BCL-2 in patients with aggressive lymphomas

“…In contrast to BCL-2, antibodies against BCL-XL, MCL-1 and survivin were not detected in the sera of our lymphoma patients, even though antibody responses against survivin (Eto et al 2007;Rohayem et al 2000;Soling et al 2007) and T-cell responses against blc-xl (Andersen et al 2005b), mcl-1 (Andersen et al 2005a) and survivin (Andersen et al 2001;Casati et al 2003;Grube et al 2007;Reker et al 2004;Schmidt et al 2003;Vence et al 2007) have been reported. The absence or low prevalence of antibodies against antiapoptosis proteins in patients with aggressive lymphomas is in line with our previous observation of weak or absent antibody responses against cancer-testis antigens in lymphoma patients (Huang et al 2002), reXecting the functional immunodeWciency frequently observed in these patients.…”

The anti-apoptotic members of the Bcl-2 family are attractive tumor-associated antigens

“…Using the IFN-g ELISPOT we demonstrated that both hematopoetic and solid cancer patients host spontaneous T-cell responses against Mcl-1-derived peptides [42][43][44]. Thus, strong and frequent CTL responses against Mcl-1 were detected in CLL patients, melanoma patients, pancreatic cancer patients and breast cancer patients, whereas no responses could be detected in healthy individuals.…”

Mcl-1 and anticancer vaccination: identification of an HLA-A2-restricted epitope

“…5 Finally, elevated level of submicron plasma membrane vesicles expressing CXCR4 has been detected in the blood and BM fluids of AML patients, providing further evidence that the CXCR4-CXCL12 axis intervenes in AML cell trafficking and tissue dissemination. 6 …”

“…4 Recently, we demonstrated that cancer patients of different origin host spontaneous T-cell responses specifically against Mcl-1-derived peptides presented in the context of the HLA-A1 and -A3 antigen. [5][6][7] However, the Mcl-1-based clinical vaccination trials await the identification of an HLA-A2-restricted epitope from Mcl-1 as HLA-A2 is the most frequent HLA-allele in the Caucasian population expressed by 50%. In the present study, the aminoacid sequence of the Mcl-1 protein was screened for the most probable HLA-A2 nona-peptide epitopes, using a cytotoxic T lymphocytes (CTL) epitope prediction algorithm available at http://www.cbs.dtu.dk/services/NetCTL/.…”