Incorporation of the Tat cell-penetrating peptide into nanofibers improves the respective antitumor immune response.

Mohammadi, Mohsen; Dehghani, Parva; Mohseninia, Atefeh; Roozbehani, Mona; Hemphill, Andrew; Hesamizadeh, Khashayar (2021). Incorporation of the Tat cell-penetrating peptide into nanofibers improves the respective antitumor immune response. Journal of cellular physiology, 236(2), pp. 1401-1417. Wiley 10.1002/jcp.29946

[img] Text
jcp.29946.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (3MB) | Request a copy

A major challenge for the development of anticancer vaccines is the induction of a safe and effective immune response, particularly mediated by CD8+ T lymphocytes, in an adjuvant-free manner. In this respect, we present a simple strategy to improve the specific CD8+ T cell responses using KFE8 nanofibers bearing a Class I (Kb)-restricted peptide epitope (called E. nanofibers) without the use of adjuvant. We demonstrate that incorporation of Tat, a cell-penetrating peptide (CPP) of the HIV transactivator protein, into E. nanofibers remarkably enhanced tumor-specific CD8+ T cell responses. E. nanofibers containing 12.5% Tat peptide (E.Tat12.5 nanofiber) increased antigen cross-presentation by bone marrow-derived dendritic cells as compared with E. nanofibers, or E. nanofibers containing 25 or 50% the Tat peptide. Uptake of KFE8.Tat12.5 nanofibers by dendritic cells (DCs) was significantly increased compared with KFE8 nanofiber lacking Tat. Peritoneal and lymph node DCs of mice immunized with E.Tat12.5 nanofibers exhibited increased presentation of the H2kb-epitope (reminiscent for cross-presentation) compared with DCs obtained from E. nanofiber vaccinated mice. Tetrameric and intracellular cytokine staining revealed that vaccination with E.Tat12.5 triggered a robust and specific CD8+ T lymphocyte response, which was more pronounced than in mice vaccinated with E. nanofibers alone. Furthermore, E.Tat12.5 nanofibers were more potent than E. nanofiber to induce antitumor immune response and tumor-infiltrating IFN-γ CD8 T lymphocyte. In terms of cancer vaccine development, we propose that harnessing the nanofiber-based vaccine platform with incorporated Tat peptide could present a simple and promising strategy to induce highly effective antitumor immune response.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology

UniBE Contributor:

Hemphill, Andrew

Subjects:

600 Technology > 630 Agriculture

ISSN:

0021-9541

Publisher:

Wiley

Language:

English

Submitter:

Andrew Hemphill

Date Deposited:

17 Feb 2021 14:27

Last Modified:

17 Feb 2021 14:34

Publisher DOI:

10.1002/jcp.29946

PubMed ID:

32686113

Uncontrolled Keywords:

CD8 cells response Tat peptide antigen cross-presentation nanofiber

BORIS DOI:

10.48350/152370

URI:

https://boris.unibe.ch/id/eprint/152370

Actions (login required)

Edit item Edit item
Provide Feedback