Induction of CD4+ T cell-dependent antitumor immunity by TAT-mediated tumor antigen delivery into dendritic cells

Helen Y. Wang, Tihui Fu, Gang Wang, Gang Zeng, Donna M. Perry-Lalley, James C. Yang, Nicholas P. Restifo, Patrick Hwu, Rong Fu Wang

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Dendritic cell-based (DC-based) immunotherapy represents a promising approach to the prevention and treatment of many diseases, including cancer, but current strategies have met with only limited success in clinical and preclinical studies. Previous studies have demonstrated that a TAT peptide derived from the HIV TAT protein has the ability to transduce peptides or proteins into various cells. Here, we describe the use of TAT-mediated delivery of T cell peptides into DCs to prolong antigen presentation and enhance T cell responses. While immunization of mice with DCs pulsed with an antigenic peptide derived from the human TRP2 protein generated partial protective immunity against B 16 tumor, immunization with DCs loaded with a TAT-TRP2 peptide resulted in complete protective immunity, as well as significant inhibition of lung metastases in a 3-day tumor model. Although both DC/TRP2 and DC/TAT-TRP2 immunization increased the number of TRP2-specific CD8+ T cells detected by Kb/TRP2 tetramers, T cell activity elicited by DC/TAT-TRP2 was three- to tenfold higher than that induced by DC/TRP2. Furthermore, both CD4+ and CD8+ T cells were required for antitumor immunity demonstrated by experiments with antibody depletion of subsets of T cells, as well as with various knockout mice. These results suggest that a TAT-mediated antigen delivery system may have important clinical applications for cancer therapy.

Original languageEnglish (US)
Pages (from-to)1463-1470
Number of pages8
JournalJournal of Clinical Investigation
Volume109
Issue number11
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Induction of CD4<sup>+</sup> T cell-dependent antitumor immunity by TAT-mediated tumor antigen delivery into dendritic cells'. Together they form a unique fingerprint.

Cite this