HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Martin, B. K. Articles by Ting, J. P.-Y. Search for Related Content PubMed PubMed Citation Articles by Martin, B. K. Articles by Ting, J. P.-Y.

Combination Gene Therapy with CD86 and the MHC Class II Transactivator in the Control of Lung Tumor Growth¹

Brian K. Martin^*, John G. Frelinger and Jenny P.-Y. Ting^2,*

^* Lineberger Comprehensive Cancer Center and Department of Microbiology-Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; and Department of Microbiology and Immunology, University of Rochester School of Medicine, Rochester, NY 14642

Early reports suggest that the costimulatory molecule CD86 (B7-2) has sporadic efficacy in tumor immunity, whereas changes in cancer immunity mediated by the MHC class II transactivator (CIITA) have not been extensively investigated. CIITA activates MHC class II expression in most cells; however, in the Line 1 lung carcinoma model system, CIITA activates MHC class I and well as class II. Here we show that CD86 is very effective in inducing a primary immune response against Line 1. Tumor cells expressing CD86 grew in only 50% of the mice injected with live cells, and those mice that developed tumors did so with significantly delayed kinetics. Furthermore, irradiated CD86-expressing Line 1 cells served as an effective tumor vaccine, demonstrating that CD86 is effective in inducing tumor immunity in the Line 1 system. These data suggest that if CIITA and CD86 cooperate, enhanced tumor immunity could be achieved. CIITA alone was mildly beneficial in slowing primary tumor growth but only when expressed at low levels. Clones expressing high levels of class II MHC grew as fast as or faster than parental tumor, and CIITA expression in a tumor vaccine assay lacked efficacy. When CIITA and CD86 were coexpressed, there was no cooperative immune protection from tumor growth. Cells that coexpress both genes also failed as a cancer vaccine, suggesting a negative role for CIITA in this lung carcinoma. These data suggest that human cancer vaccine trials utilizing CIITA gene therapy alone or in combination with CD86 should be approached with caution.

This article has been cited by other articles:

				L. Mortara, P. Castellani, R. Meazza, G. Tosi, A. De Lerma Barbaro, F. A. Procopio, A. Comes, L. Zardi, S. Ferrini, and R. S. Accolla CIITA-Induced MHC Class II Expression in Mammary Adenocarcinoma Leads to a Th1 Polarization of the Tumor Microenvironment, Tumor Rejection, and Specific Antitumor Memory. Clin. Cancer Res., June 1, 2006; 12(11): 3435 - 3443. [Abstract] [Full Text] [PDF]

				T. Yazawa, T. Ito, H. Kamma, T. Suzuki, K. Okudela, H. Hayashi, H. Horiguchi, T. Ogata, H. Mitsui, M. Ikeda, et al. Complicated Mechanisms of Class II Transactivator Transcription Deficiency in Small Cell Lung Cancer and Neuroblastoma Am. J. Pathol., July 1, 2002; 161(1): 291 - 300. [Abstract] [Full Text] [PDF]

				W. J. Magner, A. L. Kazim, C. Stewart, M. A. Romano, G. Catalano, C. Grande, N. Keiser, F. Santaniello, and T. B. Tomasi Activation of MHC Class I, II, and CD40 Gene Expression by Histone Deacetylase Inhibitors J. Immunol., December 15, 2000; 165(12): 7017 - 7024. [Abstract] [Full Text] [PDF]

				J. A. Harton and J. P.-Y. Ting Class II Transactivator: Mastering the Art of Major Histocompatibility Complex Expression Mol. Cell. Biol., September 1, 2000; 20(17): 6185 - 6194. [Full Text]