Synthesized natural peptides from amphibian skin secretions increase the efficacy of a therapeutic vaccine by recruiting more T cells to the tumour site

• Main Authors: Xuan Pan, Bowei Ma, Xinchao You, Shu Chen, Jialing Wu, Tianfang Wang, Shelley F. Walton, Jianwei Yuan, Xiaolian Wu, Guoqiang Chen, Yuejian Wang, Guoying Ni, Xiaosong Liu
• Format: Article
• Language: English
• Published: BMC 2019-07-01
• Series: BMC Complementary and Alternative Medicine
• Subjects: Caerin peptide; Therapeutic vaccine; Cervical cancer; Tumour microenvironment
• Online Access: http://link.springer.com/article/10.1186/s12906-019-2571-z

Abstract Background Therapeutic vaccines against cervical cancer remain ineffective. Previously, we demonstrated that blocking the signalling of a cytokine, interleukin 10, at the time of immunisation elicited significantly higher numbers of antigen specific T cells and inhibited tumour growth in mice. Results In the current paper, we demonstrate, in a HPV16 E6/E7 transformed TC-1 tumour mouse model, that despite increased antigen specific T cell numbers, blocking IL-10 signalling at the time of immunisation does not increase the survival time of the TC-1 tumour bearing mice compared to mice receiving the same immunisation with no IL-10 signalling blockade. Moreover, the function of tumour infiltrating T cells isolated 3 weeks post TC-1 transplantation is more suppressed than those isolated 2 weeks after tumour inoculation. We demonstrate that synthesized caerin peptides, derived from amphibian skin secretions, 1) were able to inhibit TC-1 tumour growth both in vitro and in vivo; 2) are environmentally stable; and 3) promote the secretion of pro-inflammatory interlukine-6 by TC-1 cells. Notably caerin peptides were able to increase the survival time of TC-1 tumour bearing mice after therapeutic vaccination with a HPV16E7 peptide-based vaccine containing IL-10 inhibitor, via recruiting increased levels of T cells to the tumour site. Conclusion Caerin peptides increase the efficacy of a therapeutic vaccine by recruiting more T cells to the tumour site.