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

Content Provider	PubMed Central
Author	Wang, Helen Y. Fu, Tihui Wang, Gang Zeng, Gang Perry-lalley, Donna M. Yang, James C. Restifo, Nicholas P. Hwu, Patrick Wang, Rong-fu
Copyright Year	2002
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 B16 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.
Related Links	http://dx.doi.org/10.1172/jci200215399
Ending Page	1470
Page Count	8
Starting Page	1463
File Format	PDF
ISSN	00219738
e-ISSN	15588238
Journal	The Journal of Clinical Investigation
Issue Number	11
Volume Number	109
Language	English
Publisher	American Society for Clinical Investigation
Publisher Date	2002-06-01
Access Restriction	Open
Rights Holder	American Society for Clinical Investigation
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine

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