In vivo expansion, persistence, and function of peptide vaccine-induced CD8 T cells occur independently of CD4 T cells.

Abstract:

:Significant efforts are being devoted toward the development of effective therapeutic vaccines against cancer. Specifically, well-characterized subunit vaccines, which are designed to generate antitumor cytotoxic CD8 T-cell responses. Because CD4 T cells participate at various stages of CD8 T-cell responses, it is important to study the role of CD4 T cells in the induction and persistence of antitumor CD8 T-cell responses by these vaccines. Recent evidence points to the requirement of CD4 T cells for the long-term persistence of memory CD8 T cells, which in the case of cancer immunotherapy would be critical for the prevention of tumor recurrences. The purpose of the present study was to assess whether CD4 T cells are necessary for the generation and maintenance of antigen-specific CD8 T cells induced by subunit (peptide or DNA) vaccines. We have used a vaccination strategy that combines synthetic peptides representing CD8 T-cell epitopes, a costimulatory anti-CD40 antibody and a Toll-like receptor agonist (TriVax) to generate large numbers of antigen-specific CD8 T-cell responses. Our results show that the rate of decline (clonal contraction) of the antigen-specific CD8 T cells and their functional state is not affected by the presence or absence of CD4 T cells throughout the immune response generated by TriVax. We believe that these results bear importance for the design of effective vaccination strategies against cancer.

journal_name

Cancer Res

journal_title

Cancer research

authors

Assudani D,Cho HI,DeVito N,Bradley N,Celis E

doi

10.1158/0008-5472.CAN-08-3134

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

9892-9

issue

23

eissn

0008-5472

issn

1538-7445

pii

68/23/9892

journal_volume

68

pub_type

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