title: Cyclophosphamide enhances anti-tumor effects of a fibroblast activation protein α-based DNA vaccine in tumor-bearing mice with murine breast carcinoma.
abstract: Cyclophosphamide (CY) is a DNA alkylating agent, which is widely used with other chemotherapy drugs in the treatment of various types of cancer. It can be used not only as a chemotherapeutic but also as an immunomodulatory agent to inhibit IL-10 expression and T regulatory cells (Tregs). Fibroblast activation protein α (FAPα) is expressed in cancer-associated fibroblasts in the tumor microenvironment. Immunotherapy based on FAPα, as a tumor stromal antigen, typically induces specific immune response targeting the tumor microenvironment. This study evaluated the efficacy of a previously unreported CY combination strategy to enhance the limited anti-tumor effect of a DNA vaccine targeting FAPα. The results suggested CY administration could promote the percentage of splenic CD8+T cells and decrease the proportion of CD4+CD25+Foxp3+Tregs in spleen. In tumor tissues, levels of immunosuppressive cytokines including IL-10 and CXCL-12 were also reduced. Meanwhile, the CY combination did not impair the FAPα-specific immunity induced by the DNA vaccine and further reduced tumor stromal factors. Most importantly, FAP-vaccinated mice also treated with CY chemotherapy showed a marked suppression of tumor growth (inhibition ratio =80%) and a prolongation of survival time. Thus, the combination of FAPα immunotherapy and chemotherapy with CY offers new insights into improving cancer therapies.
authors.affiliation: a National Engineering Laboratory for AIDS Vaccine, School of Life Science , Jilin University , Changchun , P. R. China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Xia
authors.affiliation: a National Engineering Laboratory for AIDS Vaccine, School of Life Science , Jilin University , Changchun , P. R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Geng
authors.affiliation: a National Engineering Laboratory for AIDS Vaccine, School of Life Science , Jilin University , Changchun , P. R. China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Zhang
authors.affiliation: a National Engineering Laboratory for AIDS Vaccine, School of Life Science , Jilin University , Changchun , P. R. China.
authors.forename: Chen-Lu
authors.initials: CL
authors.lastname: Liu
authors.affiliation: a National Engineering Laboratory for AIDS Vaccine, School of Life Science , Jilin University , Changchun , P. R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.affiliation: a National Engineering Laboratory for AIDS Vaccine, School of Life Science , Jilin University , Changchun , P. R. China.
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Lu
authors.affiliation: a National Engineering Laboratory for AIDS Vaccine, School of Life Science , Jilin University , Changchun , P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xie
authors.affiliation: a National Engineering Laboratory for AIDS Vaccine, School of Life Science , Jilin University , Changchun , P. R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: a National Engineering Laboratory for AIDS Vaccine, School of Life Science , Jilin University , Changchun , P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: a National Engineering Laboratory for AIDS Vaccine, School of Life Science , Jilin University , Changchun , P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: a National Engineering Laboratory for AIDS Vaccine, School of Life Science , Jilin University , Changchun , P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.affiliation: a National Engineering Laboratory for AIDS Vaccine, School of Life Science , Jilin University , Changchun , P. R. China.
authors.forename: Xiang-Hui
authors.initials: XH
authors.lastname: Yu
authors.affiliation: a National Engineering Laboratory for AIDS Vaccine, School of Life Science , Jilin University , Changchun , P. R. China.
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000493:pharmacokinetics*; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases / Q000276:immunology / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008565:Membrane Proteins / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012697:Serine Endopeptidases / Q000276:immunology / Q000494:pharmacology*; D019444:Vaccines, DNA / Q000276:immunology / Q000493:pharmacokinetics*; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D019496:Cancer Vaccines; D003520:Cyclophosphamide; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D019444:Vaccines, DNA; D000099167:Fibroblast Activation Protein Alpha
keywords: Cyclophosphamide; cancer combination therapy; fibroblast activation protein α; immunomodulation; tumor immunology