Harnessing self-assembling peptide nanofibers to prime robust tumor-specific CD8 T cell responses in mice

Induction of tumor-specific CD8 + T cell responses is known as a major challenge for cancer vaccine development; here we presented a strategy to improve peptide nanofibers-mounted antitumor immune responses. To this end, peptide nanofibers bearing class I (Kb)-restricted epitope (Epi-Nano) were formulated with polyethylene imine backbone (Epi-Nano-PEI), and characterized using morphological and physicochemical characterization techniques. Nanofibers were studied in terms of their uptake by antigen-presenting cells (APCs), antigen cross-presentation capacity, and cytotoxic activity. Furthermore, nanofibers were assessed by their potency to induce NLRP3 inflammasome-related cytokines and factors. Finally, the ability of nanofibers to induce tumorspecific CD8 T cells and tumor protection were investigated in tumor-bearing mice. The formulation of EpiNano with PEI led to the formation of short strand nanofibers with a positive surface charge, a low critical aggregation concentration (CAC), and an increased resistance to proteolytic degradation. Epi-Nano-PEI was significantly taken up more efficiently by antigen-presenting cells (APCs), and was more potent in crosspresentation when compared to Epi-Nano. Moreover, Epi-Nano-PEI, in comparison to Epi-Nano, efficiently upregulated the expression of NLRP3, caspase-1, IL-1b, IL18 and IL-6. Cell viability analysis showed that formulation of PEI with Epi-Nano not only abolished its cytotoxic activity, but surprisingly induced macrophage proliferation. Furthermore, it demonstrated that Epi-Nano-PEI triggered robust antigen-specific CD8+ T cell responses, and induced maximum antitumor response (tumor growth inhibition and prolonged survival) in tumor-bearing mice that were significantly higher compared to Epi-Nano. Taken together, the formulation of EpiNano with PEI is suggested as a promising strategy to improve nanofibers-mounted antitumor immune response.

Automated summary

This study presents a strategy to enhance peptide nanofibers-mounted antitumor immune response by formulating peptide nanofibers with polyethylene imine. The formulated nanofibers showed increased efficiency in uptake by antigen-presenting cells, enhanced antigen cross-presentation capacity, and the ability to induce robust antigen-specific CD8+ T cell responses. The formulation also led to maximum antitumor response in tumor-bearing mice.