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

Abstract

BackgroundVaccines 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.PurposeThis 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.MethodsA 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.ResultsPreventive 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.ConclusionThe 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.

HPV Involvement in the Tumor Microenvironment and Immune Treatment in Head and Neck Squamous Cell Carcinomas

“…Recently, Ryan and co-authors demonstrate that STAT1 is an essential mediator of the antitumor response through the inhibition of myeloid derived suppressor cell accumulation and promotion of T-cell mediated immune responses in murine HPV− head and neck squamous cell carcinoma [103]. Many other studies were conducted with the aim to investigate antitumor effects in HPV+ murine models, so Li et al recently published that their candidate vaccine against HPV16E7 significantly reduced Treg and MDSCs infiltration in mouse genital tumors [104,105]. Given the creation of a new immunocompetent mouse model of HPV16+ head and neck squamous cell carcinoma [106], this promising vaccination strategy should be considered and tested for the treatment of HPV+ oropharyngeal SCC.…”

Multivalent display of chemical signals on self‐assembled peptide scaffolds

“…[77] Induction of tumor-specific cellular immunity via therapeutic vaccination presents a promising strategy for cancer targets, such as human papillomavirus (HPV). In a study done by Li et al, [72] Q11…”

“…Induction of tumor‐specific cellular immunity via therapeutic vaccination presents a promising strategy for cancer targets, such as human papillomavirus (HPV). In a study done by Li et al ., [ 72 ] Q11 nanofibers displaying fragments of the E7 oncoprotein, E7 44‐62 , were used as an immunomodulatory agent for HPV tumors and almost completely hindered tumor growth when delivered subcutaneously. Inhibition of growth was significantly higher in mice immunized with the assembled nanofibers compared to unassembled E7 44‐62 ‐Q11.…”

Self-adjuvanting cancer nanovaccines

“…Cancer vaccines containing a variable number of full-length tandem repeat domains of MUC1 and Q11 can trigger a significant immune response, including complement-dependent cytotoxicity against MCF-7 cells [ 129 ]. Nanofibers prepared by chemically linking the HPV16 E7 peptide and the N-terminus of the self-assembling peptide Q11 also prevent the formation of transplanted TC-1 tumors and suppress the growth of established TC-1 tumors [ 130 ]. Similarly, peptide Coil29 (QARILEADAEILRAYARILEAHAEILRAD), a peptide composed of almost complete α-helical structures, also induces strong humoral and cellular immune responses without adjuvant [ 131 ].…”