title: Low-dose paclitaxel improves the therapeutic efficacy of recombinant adenovirus encoding CCL21 chemokine against murine cancer.
abstract: Secondary lymphoid tissue chemokine (SLC/CCL21), one of the CC chemokines, exerts potent antitumor immunity by co-localizing T cells and dendritic cells at the tumor site and is currently tested against human solid tumors. Here, we investigated whether the combination of recombinant adenovirus encoding murine CCL21 (Ad-mCCL21) with low-dose paclitaxel would improve therapeutic efficacy against murine cancer. Immunocompetent mice bearing B16-F10 melanoma or 4T1 breast carcinoma were treated with either Ad-mCCL21, paclitaxel, or both agents together. Our results showed that Ad-mCCL21 + low-dose paclitaxel more effectively reduced the growth of tumors as compared with either treatment alone and significantly prolonged survival time of the tumor-bearing animals. These antitumor effects of the combined therapy were linked to altered cytokine network at the tumor site, enhanced apoptosis of tumor cells, and decreased formation of new vessels in tumors. Importantly, the combined therapy elicited a strong therapeutic antitumor immunity, which could be partly abrogated by the depletion of CD4(+) or CD8(+) T lymphocytes. Collectively, these preclinical evaluations may provide a combined strategy for antitumor immunity and should be considered for testing in clinical trials.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China; National Institutes for Food and Drug Control, Beijing, China; Chengdu Institute of Biological Products Co., Ltd, Chengdu, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Shan
authors.initials: S
authors.lastname: Luo
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Wen
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Li
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Wang
authors.forename: Li-Cheng
authors.initials: LC
authors.lastname: Du
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Jiao
authors.initials: J
authors.lastname: Tang
authors.forename: Da-Bing
authors.initials: DB
authors.lastname: Yang
authors.forename: Huo-Zhen
authors.initials: HZ
authors.lastname: Hu
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D054421:Chemokine CCL21 / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D006801:Humans; D008546:Melanoma, Experimental; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009389:Neovascularization, Pathologic; D017239:Paclitaxel / Q000494:pharmacology*; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D054421:Chemokine CCL21; D016207:Cytokines; D017239:Paclitaxel
keywords: Angiogenesis; CCL21; cytotoxic T lymphocytes; immunotherapy; paclitaxel