Induction of HCA587-specific antitumor immunity with HCA587 protein formulated with CpG and ISCOM in mice.
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-γ-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-γ. These results indicate that HCA587 protein vaccine possesses evident antitumor activity in a mouse model and holds promise for treatment of human cancers.
Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing, People's Republic of China.
Juanjuan
J
Chen
Lijie
L
Zhang
Weigang
W
Wen
Jiaqing
J
Hao
Pumei
P
Zeng
Xiaoping
X
Qian
Yu
Y
Zhang
Yanhui
Y
Yin
D000276:Adjuvants, Immunologic; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000494:pharmacology; D019496:Cancer Vaccines; D016207:Cytokines / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D016882:ISCOMs / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007371:Interferon-gamma / Q000235:genetics; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000276:immunology* / Q000494:pharmacology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D016207:Cytokines; D016882:ISCOMs; C405429:MAGEC2 protein, human; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; D007371:Interferon-gamma