Indirect stimulation of the immune system against breast adenocarcinoma in mice using an anti-angiogenic peptide

Introduction: Angiogenesis inhibitors are an important class of anti-cancer drugs and endostatin is one of these drugs that inhibit the growth of different kinds of tumors. In addition, in recent years application of peptide drugs is increasing because of their advantages like penetration into tissues and the less cost of production comparing to the proteins and antibodies. Potent anti-angiogenic and anti-tumor activities of an engineered peptide derived from endostatin have been shown recently but its immunogenicity has never been studied. Therefore in the present study, the effect of this peptide on the immune system of normal and breast adenocarcinoma-bearing mice was investigated. Methods: 36 female BALB/c mice were divided into treatment including normal and tumor-bearing mice and control groups and at the end of the study the level of cytokines TNF-α, IL-4, IL-10, IL-17 and IFN-γ secreted from splenocytes of mice were assessed using ELISA kit. In addition, tumor volume was measured by a caliper. Results: Based on the results, the level of mentioned cytokines in normal mice did not show statistical significant difference between mice treated with 1 and 5 mg/kg/day peptide and control group but in breast adenocarcinoma-bearing mice the difference of the level of five cytokines was statistically significant in comparison to the control especially in group treated with 1 mg/kg/day. Furthermore, peptide could prevent the growth of breast tumor, remarkably. Conclusion: we can propose in one hand, the peptide derived from endostatin is not immunogenic for normal cells and On the other hand, this peptide in addition to its anti-angiogenic mechanisms for inhibiting the tumor growth, activates immune system especially Th2 immune cells against cancer cells. So, it can be considered as a vaccine adjuvant for cancer immunotherapy, however, additional experiments are required.

Keywords:

Angiogenesis inhibitor , Engineered peptide , Immunogenicity , Breast adenocarcinoma , Cancer immunotherapy