Cyclophosphamide enhances anti-tumor effects of a fibroblast activation protein α-based DNA vaccine in tumor-bearing mice with murine breast carcinoma.

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Cyclophosphamide enhances anti-tumor effects of a fibroblast activation protein α-based DNA vaccine in tumor-bearing mice with murine breast carcinoma.

Immunopharmacol Immunotoxicol. 2016 Dec 22;:1-8

Authors: Xia Q, Geng F, Zhang FF, Liu CL, Xu P, Lu ZZ, Xie Y, Sun B, Wu H, Yu B, Kong W, Yu XH, Zhang HH

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.

PMID: 28004985 [PubMed - as supplied by publisher]

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