title: Low-dose paclitaxel enhances the anti-tumor efficacy of GM-CSF surface-modified whole-tumor-cell vaccine in mouse model of prostate cancer.
abstract: Chemotherapy combined with a tumor vaccine is an attractive approach in cancer therapy. This study was designed to investigate the optimal schedule and mechanisms of action of a novel GM-CSF (granulocyte-macrophage colony-stimulating factor) surface-modified tumor-cell vaccine in combination with paclitaxel in the treatment of mouse RM-1 prostate cancer. First, the anti-tumor efficiencies of various dosage of paclitaxel (4, 20, 40 mg/kg) in combination with the vaccine in different administration sequences were examined in the mouse RM-1 prostate cancer model. Then, the in vivo and in vitro effects of various dosage of paclitaxel on RM-1 cells, T cells, and DCs (dendritic cells) were evaluated. The results showed that: (a) the GM-CSF-surface-modified tumor-cell vaccine was more potent at inducing the uptake of tumor antigens by DCs than irradiated tumor cells plus free GM-CSF; (b) 4 mg/kg paclitaxel combined with the GM-CSF-surface-modified tumor-cell vaccine was the most effective at enhancing tumor regression in RM-1 prostate cancer mice when the vaccine was administrated 2 days after paclitaxel; and (c) administration of 4 mg/kg paclitaxel followed by the vaccine induced the highest degree of CD8(+) T-cell infiltration in tumor tissue, suggesting that the induction of tumor-specific immune response had occurred. These findings suggested that the GM-CSF-surface-modified tumor-cell vaccine may have potential clinical benefit for patients with prostate cancer when it is combined with paclitaxel. Furthermore, the effect of immunochemotherapy depends on careful selection of paclitaxel dosage and the sequence of paclitaxel/vaccine administration.
authors.affiliation: Zhejiang Provincial Key Lab for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, University Park, Wenzhou, China.
authors.forename: Qiushan
authors.initials: Q
authors.lastname: He
authors.forename: Jinlong
authors.initials: J
authors.lastname: Li
authors.forename: Weihua
authors.initials: W
authors.lastname: Yin
authors.forename: Zhichun
authors.initials: Z
authors.lastname: Song
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Tienan
authors.initials: T
authors.lastname: Yi
authors.forename: Jia
authors.initials: J
authors.lastname: Tang
authors.forename: Demin
authors.initials: D
authors.lastname: Wu
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Xiaoren
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Hu
authors.forename: Jimin
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D000972:Antineoplastic Agents, Phytogenic; D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017239:Paclitaxel