title: Cancer immunotherapy using a potent immunodominant CTL epitope.
abstract: Immunotherapy has emerged as a promising approach that can be used in conjunction with conventional chemotherapy and radiotherapy to further improve the survival rate of patients with advanced cancer. We have recently shown in previous studies that chemotherapy and radiation therapy can alter the tumor microenvironment and allow intratumoral vaccination to prime the adaptive immune system leading to the generation of antigen-specific cell-mediated immune responses. Here, we investigated whether intratumoral injection of a foreign immunodominant peptide (GP33) and the adjuvant CpG into tumors following cisplatin chemotherapy could lead to potent antitumor effects and antigen-specific cell-mediated immune responses. We observed that treatment with all three agents produced the most potent antitumor effects compared to pairwise combinations. Moreover, treatment with cisplatin, CpG and GP33 was able to control tumors at a distant site, indicating that our approach is able to induce cross-presentation of the tumor antigen. Treatment with cisplatin, CpG and GP33 also enhanced the generation of GP33-specific and E7-specific CD8+ T cells and decreased the number of MDSCs in tumor loci, a process found to be mediated by the Fas-FasL apoptosis pathway. The treatment regimen presented here represents a universal approach to cancer control.
authors.affiliation: Pharmacy School of Fudan University, Shanghai, China; Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China; Departments of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Shanghai, China; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, United States.
authors.forename: Liwen
authors.initials: L
authors.lastname: Song
authors.affiliation: General Surgery and Surgical Intensive Care, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Ming-Chieh
authors.initials: MC
authors.lastname: Yang
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, United States.
authors.forename: Jayne
authors.initials: J
authors.lastname: Knoff
authors.affiliation: Departments of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Shanghai, China.
authors.forename: Zu-Yue
authors.initials: ZY
authors.lastname: Sun
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, United States; Departments of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, MD, United States; Departments of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD, United States; Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, United States.
authors.forename: T-C
authors.initials: TC
authors.lastname: Wu
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, United States; Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, United States. Electronic address: chung2@jhmi.edu.
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002945:Cisplatin / Q000494:pharmacology; D045142:Cross-Priming; D005260:Female; D007111:Immunity, Cellular; D016056:Immunodominant Epitopes / Q000276:immunology*; D007167:Immunotherapy; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D050725:Papillomavirus E7 Proteins / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D016056:Immunodominant Epitopes; D009838:Oligodeoxyribonucleotides; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D002945:Cisplatin
keywords: Cisplatin; Immunodominant CTL epitope; Immunotherapy