4.3 Article

Self-Adjuvanting Therapeutic Peptide-Based Vaccine Induce CD8(+) Cytotoxic T Lymphocyte Responses in a Murine Human Papillomavirus Tumor Model

Journal

CURRENT DRUG DELIVERY
Volume 12, Issue 1, Pages 3-8

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1567201811666141001155729

Keywords

Cytotoxic T lymphocyte (CTL) responses; human papillomavirus; peptide subunit vaccine; polyacrylate; self-adjuvanting; star-polymer; therapeutic anticancer vaccine

Funding

  1. National Health and Medical Research Council [NHMRC 1006454]

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Vaccine candidates for the treatment of human papillomavirus (HPV)-associated cancers are aimed to activate T-cells and induce development of cytotoxic anti-tumor specific responses. Peptide epitopes derived from HPV-16 E7 oncogenic protein have been identified as promising antigens for vaccine development. However, peptide-based antigens alone elicit poor cytotoxic T lymphocyte (CTL) responses and need to be formulated with an adjuvant (immunostimulant) to achieve the desired immune responses. We have reported the ability of polyacrylate 4-arm star-polymer (S4) conjugated with HPV-16 E7(44-57) (8Q(min)) epitope to reduce and eradicate TC-1 tumor in the mouse model. Herein, we have studied the mechanism of induction of immune responses by this polymer-peptide conjugate and found prompt uptake of conjugate by antigen presenting cells, stimulating stronger CD8(+) rather than CD4(+) or NK cell responses.

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