title: Enhancing the treatment effect on melanoma by heat shock protein 70-peptide complexes purified from human melanoma cell lines.
abstract: Dendritic cell (DC) vaccines are currently one of the most effective approaches to treat melanoma. The immunogenicity of antigens loaded into DCs determines the treatment effects. Patients treated with autologous antigen-loaded DC vaccines achieve the best therapeutic effects. In China, most melanoma patients cannot access their autologous antigens because of formalin treatment of tumor tissue after surgery. In the present study, we purified heat shock protein 70 (HSP70)-peptide complexes (PCs) from human melanoma cell lines A375, A875, M21, M14, WM‑35, and SK‑HEL‑1. We named the purified product as M‑HSP70‑PCs, and determined its immunological activities. Autologous HSP70‑PCs purified from primary tumor cells of melanoma patients (nine cases) were used as controls. These two kinds of tumor antigenic complexes loaded into DCs were used to stimulate an antitumor response against tumor cells in the corresponding patients. Mature DCs pulsed with M‑HSP70‑PCs stimulated autologous T cells to secrete the same levels of type I cytokines compared with the autologous HSP70‑PCs. Moreover, DCs pulsed with M‑HSP70‑PCs induced CD8+ T cells with an equal ability to kill melanoma cells from patients compared with autologous HSP70‑PCs. Next, we used these PC‑pulsed autologous DCs and induced autologous specific CD8+ T cells to treat one patient with melanoma of the nasal skin and lung metastasis. The treatment achieved a good effect after six cycles. These findings provide a new direction for DC-based immunotherapy for melanoma patients who cannot access autologous antigens.
authors.affiliation: Cancer Center, Beijing Key Lab of Therapeutic Cancer Vaccines, Affiliated Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Oncology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia 010017, P.R. China.
authors.forename: Weishi
authors.initials: W
authors.lastname: Gao
authors.affiliation: Inner Mongolia Red Cross Blood Center, Hohhot, Inner Mongolia 010010, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Cancer Center, Beijing Key Lab of Therapeutic Cancer Vaccines, Affiliated Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China.
authors.forename: Nier
authors.initials: N
authors.lastname: Cha
authors.affiliation: Cancer Center, Beijing Key Lab of Therapeutic Cancer Vaccines, Affiliated Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Oncology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia 010017, P.R. China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Oncology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia 010017, P.R. China.
authors.forename: Bingping
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Oncology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia 010017, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Ren
authors.affiliation: Cancer Center, Beijing Key Lab of Therapeutic Cancer Vaccines, Affiliated Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
mesh_terms: D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D001324:Autoantigens; D019496:Cancer Vaccines; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D010455:Peptides