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

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.

• 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
• Journal: BMC complementary and alternative medicine (BMC Complement Altern Med) Vol. 19 Issue 1 Pg. 163 (Jul 06 2019) ISSN: 1472-6882 [Electronic] England
• PMID: 31277636 (Publication Type: Journal Article)

Chemical References

• Amphibian Proteins
• Antimicrobial Cationic Peptides
• Cancer Vaccines
• IL10 protein, mouse
• Interleukin-6
• caerin 1.1, Anura
• caerin 1.9 protein, Litoria
• interleukin-6, mouse
• Interleukin-10

Topics

• Amphibian Proteins (pharmacology, therapeutic use)
• Animals
• Antimicrobial Cationic Peptides (pharmacology, therapeutic use)
• Cancer Vaccines (pharmacology, therapeutic use)
• Drug Screening Assays, Antitumor
• Female
• HeLa Cells
• Humans
• Interleukin-10 (antagonists & inhibitors)
• Interleukin-6 (metabolism)
• Lymphocytes, Tumor-Infiltrating (drug effects, metabolism)
• Mice, Inbred C57BL
• Neoplasm Transplantation
• Neoplasms, Experimental (drug therapy)
• T-Lymphocytes (drug effects, metabolism)