The cancer/testis antigen HCA587 (also known as MAGE-C2), one of the most immunogenic tumor antigens, is overexpressed in a wide spectrum of malignant tumors and can serve as a target for immunotherapy. In this study, we synthesized 14 overlapping (25-35 amino acids) long peptides representing the sequence of the most immunogenic part of the HCA587 protein and evaluated the antigen-specific immune responses and antitumor effects generated by immunization with the synthetic long peptide (SLP) vaccine in a mouse model. HCA587 SLPs in combination with adjuvants CFA and CpG ODN induced potent T-cell responses, which were dominated by type 1 cytokine IFN-?-producing CD4(+) T cells as measured by ELISPOT and intracellular cytokine staining assay. Moreover, HCA587 SLP vaccination conferred protection against challenge with HCA587-expressing B16 melanoma in a therapeutic setting. Our findings may provide a scientific basis for the use of HCA587-derived long overlapping peptide vaccine for the treatment of patients with cancer in future clinical trials.
Riboflavin is the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), essential cofactors for many metabolic enzymes that catalyze a variety of biochemical reactions. Previously we showed that free flavin (riboflavin, FMN, and FAD) concentrations were decreased in leaves of transgenic Arabidopsis plants expressing a turtle riboflavin-binding protein (RfBP). Here, we report that flavin downregulation by RfBP induces the early flowering phenotype and enhances expression of floral promoting photoperiod genes.
The cancer testis antigen HCA587 is an attractive candidate for T cell-based immunotherapy because it is overexpressed in a wide spectrum of malignant tumors but not normal tissues, except testis. Several CTL epitopes derived from HCA587 have been described. Our aim was to identify helper T lymphocyte epitopes of HCA587 for the optimization of T cell-based immunotherapies against HCA587-expressing tumors. Candidate helper T lymphocyte epitopes for HCA587 were predicted using the SYFPEITHI algorithm and were tested for their ability to induce helper T lymphocyte responses by in vitro peptide vaccination of CD4(+) T lymphocytes from healthy individuals and hepatocellular carcinoma patients. Four CD4(+) T-cell epitopes for HCA587 (p43-57, p145-159, p186-200 and p249-263) were identified. Among them, the p43-57 epitope was shown to be naturally processed and presented by HCA587-expressing tumor cells as well as autologous dendritic cells pulsed with whole-protein HCA587. Notably, this epitope behaved as a promiscuous T-cell epitope as it stimulated T cells in the context of more than one HLA class II allele. Thus, p43-57 is the first HCA587-derived major histocompatibility complex class II-restricted epitope to fulfil all prerequisites for use as a peptide vaccine in patients with HCA587-expressing tumors.
HCA587 (also known as MAGE-C2) is a "cancer-testis" antigen highly expressed in a number of malignancies with unique immunological properties, making it a promising target for tumor immunotherapy. In this report, we demonstrated that HCA587 protein, when formulated with adjuvants CpG-containing oligodeoxynucleotides (CpG ODN) and ISCOM, was capable of inducing a potent cellular and humoral immune response as indicated by the presence of a large number of HCA587-specific, IFN-?-producing CD4(+) T cells and high levels of HCA587-specific antibodies. More importantly, vaccination with HCA587 conferred protection against challenge with HCA587-expressing B16 melanoma in prophylactic and therapeutic settings. In analysis of the mechanisms underlying the protective effect, we showed that the vaccination was followed by enhanced accumulation of tumor-infiltrating lymphocytes (TILs) with enrichment of conventional CD4(+) T cells but reduced representation of Treg cells. Further, the antitumor effect was largely abrogated in mice either depleted of CD4(+) T cells or deficient for IFN-?. These results indicate that HCA587 protein vaccine possesses evident antitumor activity in a mouse model and holds promise for treatment of human cancers.
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