| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,||
* Immunology/Immunotherapy Program, Medical College of Georgia Cancer Center,
Department of Medicine, and
Department of Pediatrics, Medical College of Georgia, Augusta, GA 30912;
Harvard College, Harvard University, Cambridge, MA 02138;
¶ Department of Surgery, University of Chicago, Maywood, IL 60153; and
|| Department of Immunology, Southern Medical University, Guangzhou, China
Recombinant lentivector immunization has been demonstrated to induce potent CD8 T cell responses in vivo. In this study, we investigated whether lentivector delivering a self/tumor Ag, tyrosinase related protein 1 (TRP1), could stimulate effective antitumor T cell responses. We found that immunization with lentivector expressing mutated TRP1 Ag elicited potent CD8 T cell responses against multiple TRP1 epitopes. Importantly, the activated CD8 T cells effectively recognize wild-type TRP1 epitopes. At peak times, as many as 10% of CD8 T cells were effector cells against TRP1 Ag. These cells killed wild-type TRP1 peptide-pulsed target cells in vivo and produced IFN-
after ex vivo stimulation. The CD8 T cell responses were long-lasting (3–4 wk). Immunized mice were protected from B16 tumor cell challenge. In a therapeutic setting, lentivector immunization induced potent CD8 T cell responses in tumor bearing mice. The number of infiltrating T cells and the ratio of CD8/CD4 were dramatically increased in the tumors of immunized mice. The tumor-infiltrating CD8 T cells were functional and produced IFN-. The potent CD8 T cell responses stimulated by lentivector immunization eliminated small 3-day s.c. B16 tumors and strongly inhibited the growth of more established 5-day tumors. These studies demonstrate that genetic immunization with lentivector expressing mutated self/tumor Ag can generate potent CD8 T cell immune responses and antitumor immunity that prevent and inhibit B16 tumor growth, suggesting that lentivector immunization has the potential for tumor immunotherapy and immune prevention.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Research in this study was supported by National Institutes of Health Grant R01 CA16444 and the Distinguished Investigator Fund from Georgia Research Alliance to Y.H.
2 Address correspondence and reprint requests to Dr. Yukai He, CN-4150, Medical College of Georgia Cancer Center, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912. E-mail address: yhe{at}mcg.edu
3 Abbreviations used in this paper: TRP1, tyrosinase related protein 1; MHC I, MHC class I; DC, dendritic cell; muTRP1, mutated tyrosinase related protein 1; wtTRP1, wild-type tyrosinase related protein 1; TU, transducing unit; TIL, tumor-infiltrating T cell; wt455, wtTRP1 peptide 455; MFI, mean fluorescence intensity.
This article has been cited by other articles:
|
|
 |
|
  M. D. Sharma, D.-Y. Hou, Y. Liu, P. A. Koni, R. Metz, P. Chandler, A. L. Mellor, Y. He, and D. H. Munn Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes Blood, June 11, 2009; 113(24): 6102 - 6111. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
