Polyclonal Rabbit Anti-Cancer-Associated Fibroblasts Globulins Induce Cancer Cells Apoptosis and Inhibit Tumor Growth.

Abstract

Cancer-associated fibroblasts (CAFs) constitute a major component of the tumor microenvironment. CAFs regulated the growth and development, invasion and metastasis of primary tumors, as well as response to treatment. Recent studies indicated that monoclonal antibody therapies had limited success, thus more effective polyclonal antibodies (Poly Abs) is urgently needed. Poly Abs is a possible alternative because they target multiple antigens simultaneously. In this report, we prepared Poly Abs by immunizing rabbits with the bFGF-activated fibroblasts. The Poly Abs inhibited the cancer cells proliferation as revealed by MTT analysis. The Poly Abs induced apoptosis as indicated by flow cytometric analysis, and microscopic observation of apoptotic changes in morphology. Compared with the control IgG, Poly Abs significantly inhibited tumor cells migration as indicated by wound healing and transwell analysis in vitro, and lung metastasis analysis in vivo. Serial intravenous injections of Poly Abs inhibited tumor growth in mice bearing murine CT26 colon carcinoma. Ki67 analysis indicated that Poly Abs significantly inhibited tumor cells proliferation, as compared to control Ig G treatments. Our findings suggested that Poly Abs was an effective agent for apoptosis induction, migration and metastasis inhibition. The Poly Abs may be useful as a safe anticancer agent for cancer immunotherapy in the future.