title: Active immunotherapy for mouse breast cancer with irradiated whole-cell             vaccine expressing VEGFR2.
abstract: As tumor-associated antigens are not well characterized for the majority             of human tumors, polyvalent vaccines prepared with whole-tumor antigens are an             attractive approach for tumor vaccination. Vascular endothelial growth factor             receptor-2 (VEGFR2), as a model antigen with which to explore the feasibility             of immunotherapy, has shown great promise as a tumor vaccine. However, the efficacy             of immunotherapy is often not ideal when used alone. In this study, we explored             the therapeutic efficacy of an irradiated AdVEGFR2-infected cell vaccine-based             immunotherapy in the weakly immunogenic and highly metastatic 4T1 murine mammary             cancer model. An adenovirus encoding the VEGFR2 gene (AdVEGFR2) was constructed.             Lethally irradiated, virus-infected 4T1 cells were used as vaccines. Vaccination             with lethally irradiated AdVEGFR2-infected 4T1 cells inhibited subsequent tumor             growth and pulmonary metastasis compared with challenge inoculations. Angiogenesis             was inhibited, and the number of CD8+ T lymphocytes was increased within the tumors.             Antitumor activity was also caused by the adoptive transfer of isolated spleen             lymphocytes. In vitro, the expression of HMGB1 and HSP70 in the AdVEGFR2‑infected             4T1 cells was increased, and was involved in the activation of tumor antigen-speciﬁc             T-cell immunity. Our results indicate that the immunotherapy based on irradiated             AdVEGFR2-infected whole-cancer cell vaccines may be a potentially effective strategy             for 4T1 cancer treatment.
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, PR China.
authors: Heng-Xiu
authors: HX
authors: Yan
authors: Ping
authors: P
authors: Cheng
authors: Hai-Yan
authors: HY
authors: Wei
authors: Guo-Bo
authors: GB
authors: Shen
authors: Li-Xin
authors: LX
authors: Fu
authors: Jie
authors: J
authors: Ni
authors: Yang
authors: Y
authors: Wu
authors: Yu-Quan
authors: YQ
authors: Wei
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000528:radiation effects; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage*; D005260:Female; D018226:Fibroadenoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005822:Genetic Vectors; D006801:Humans; D016233:Immunotherapy, Active; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000276:immunology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000008:administration & dosage / Q000235:genetics*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D040301:Vascular Endothelial Growth Factor Receptor-2