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

Mohseninia, Atefeh and Dehghani, Parva and Bargahi, Afshar and Rad-Malekshahi, Mazda and Rahimikian, Raha and Movahed, Ali and Farzaneh, Mohammad Reza and Mohammadi, Mohsen (2022) Harnessing self-assembling peptide nanofibers to prime robust tumor-specific CD8 T cell responses in mice. International Immunopharmacology, 104. ISSN 1567-5769

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Official URL: https://www.sciencedirect.com/science/article/pii/...


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 tumor-specific CD8 T cells and tumor protection were investigated in tumor-bearing mice. The formulation of Epi-Nano 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 cross-presentation when compared to Epi-Nano. Moreover, Epi-Nano-PEI, in comparison to Epi-Nano, efficiently up-regulated 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 Epi-Nano with PEI is suggested as a promising strategy to improve nanofibers-mounted antitumor immune response.

Item Type: Article
Subjects: QU Biochemistry
Divisions: Faculty of Medicin > Department of Biochemistry
Depositing User: خدیجه شبانکاره
Date Deposited: 02 Nov 2022 06:17
Last Modified: 02 Nov 2022 06:17
URI: http://eprints.bpums.ac.ir/id/eprint/9613

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