Cancer immunotherapy using novel tumor-associated antigenic peptides identified by genome-wide cDNA microarray analyses.
Recent genome-wide cDNA microarray analysis of gene expression profiles in comprehensive tumor types coupled with isolation of cancer tissues by laser-microbeam microdissection have revealed ideal tumor-associated antigens (TAAs) that are frequently overexpressed in various cancers including head and neck squamous cell cancer (HNSCC) and lung cancer, but not in most normal tissues except for testis, placenta, and fetal organs. Preclinical studies using HLA-transgenic mice and human T cells in vitro showed that TAA-derived CTL-epitope short peptides (SPs) are highly immunogenic and induce HLA-A2 or -A24-restricted CTLs. Based on the accumulated evidence, we carried out a phase II clinical trial of the TAA-SP vaccine in advanced 37 HNSCC patients. This study showed a significant induction of TAA-specific CTLs in the majority of patients without serious adverse effects. Importantly, clinical responses including a complete response were observed in this study. Another phase II clinical trial of therapeutic TAA-SP vaccine, designed to evaluate the ability of prevention of recurrence, is ongoing in HNSCC patients who have received curative operations. Further studies in human preclinical studies and in vivo studies using HLA class I transgenic mice showed TAA-derived long peptides (TAA-LPs) have the capacity to induce not only promiscuous HLA class II-restricted CD4(+) T helper type 1 cells but also tumor-specific CTLs through a cross-presentation mechanism. Moreover, we observed an augmentation of TAA-LP-specific T helper type 1 cell responses and tumor antigen-spreading in HNSCC patients vaccinated with TAA-SPs. This accumulated evidence suggests that therapeutic TAA-SPs and LPs vaccines may provide a promising cancer immunotherapy.
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Yasuharu
Y
Nishimura
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.|Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Yusuke
Y
Tomita
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.|Department of Oral and Maxillofacial Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Akira
A
Yuno
Department of Oral and Maxillofacial Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.|Itoh Maxillofacial Hospital, Kumamoto, Japan.
Yoshihiro
Y
Yoshitake
Department of Oral and Maxillofacial Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.|Itoh Maxillofacial Hospital, Kumamoto, Japan.
Masanori
M
Shinohara
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000628:therapy; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D000939:Epitopes / Q000276:immunology; D055106:Genome-Wide Association Study / Q000379:methods; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000628:therapy; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008822:Mice, Transgenic; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000235:genetics / Q000276:immunology; D000077195:Squamous Cell Carcinoma of Head and Neck; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D000951:Antigens, Neoplasm; D000939:Epitopes; D010455:Peptides
CTL epitope; Cancer immunotherapy; cDNA microarray analysis; helper T-cell epitope; tumor-associated antigen