Self-Assembled Nanofibers Elicit Potent HPV16 E7-Specific Cellular Immunity And Abolish Established TC-1 Graft Tumor

Abstract

Background: Vaccines are one of the most promising strategies for immunotherapy of HPV associated tumors; however, they generally lack significant clinical efficacy at present. This inefficacy might be due to inefficient generation of anti-tumor cellular immune responses. Purpose: This study aimed to assess the potential of using self-assembled nanofibers as a new vaccine platform to elicit potent HPV antigen-specific anti-tumor immunity. Methods: A HPV16 E744-62 peptide was chemically appended to the N terminus of self-assembling peptide Q11. The nanofibers were prepared and used to immunize mice through a preventive or therapeutic strategy in a TC-1 graft tumor model. Results: Preventive immunization with nanofibers almost completely suppressed the growth of primarily grafted TC-1 tumors and even a re-challenge of tumor cells after a six-week rest. Therapeutic immunization significantly increased the levels of effector Th1 cells, CTLs and the cytokines IFN-γ and TNF-α in E7 peptide-stimulated splenocytes, and the immunization reduced Th2, MDSC and IL-4 contents compared to the controls. The nanofiber immunization significantly suppressed the growth of established tumors and achieved 66.7% and 50% tumor-free in mice carrying 2–3 mm tumors and even larger tumors with a diameter of 5–6 mm respectively. In addition, the nanofibers were more efficient than the corresponding unassembled peptides for the treatment of established larger size tumors. Conclusion: The results indicated that self-assembling nanofibers could elicit robust HPV antigen -specific anti-tumor cellular immunity and are a potent antigen delivery system for HPV related tumor vaccines.