This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, J. Articles by Gilboa, E. Search for Related Content PubMed PubMed Citation Articles by Lee, J. Articles by Gilboa, E.

Tumor Immunotherapy Targeting Fibroblast Activation Protein, a Product Expressed in Tumor-Associated Fibroblasts

Center for Translational Research, Department of Surgery, Duke University Medical Center, Durham, North Carolina

Requests for reprints: Eli Gilboa, Department of Surgery, Duke University Medical Center, Box 2601, Durham, NC 27710. Phone: 919-684-6465; Fax: 919-668-2587; E-mail: e.gilboa{at}cgct.duke.edu.

Murine studies have shown that immunologic targeting of the tumor vasculature, a key element of the tumor stroma, can lead to protective immunity in the absence of significant pathology. In the current study, we expand the scope of stroma-targeted immunotherapy to antigens expressed in tumor-associated fibroblasts, the predominant component of the stroma in most types of cancer. Mice were immunized against fibroblast activation protein (FAP), a product up-regulated in tumor-associated fibroblasts, using dendritic cells transfected with FAP mRNA. Using melanoma, carcinoma, and lymphoma models, we show that tumor growth was inhibited in tumor-bearing mice vaccinated against FAP and that the magnitude of the antitumor response was comparable to that of vaccination against tumor cell–expressed antigens. Both s.c. implanted tumors and lung metastases were susceptible to anti-FAP immunotherapy. The antitumor response could be further enhanced by augmenting the CD4+ T-cell arm of the anti-FAP immune response, achieved by using a lysosomal targeting sequence to redirect the translated FAP product into the class II presentation pathway, or by covaccination against FAP and a tumor cell–expressed antigen, tyrosinase-related protein 2. No morbidity or mortality was associated with anti-FAP vaccination except for a small delay in wound healing. The study suggests that FAP, a product which is preferentially expressed in tumor-associated fibroblasts, could function as a tumor rejection antigen in a broad range of cancers.

This article has been cited by other articles:

				M. A. Cheever, J. P. Allison, A. S. Ferris, O. J. Finn, B. M. Hastings, T. T. Hecht, I. Mellman, S. A. Prindiville, J. L. Viner, L. M. Weiner, et al. The Prioritization of Cancer Antigens: A National Cancer Institute Pilot Project for the Acceleration of Translational Research Clin. Cancer Res., September 1, 2009; 15(17): 5323 - 5337. [Abstract] [Full Text] [PDF]

				S.-i. Fujii, A. Goto, and K. Shimizu Antigen mRNA-transfected, allogeneic fibroblasts loaded with NKT-cell ligand confer antitumor immunity Blood, April 30, 2009; 113(18): 4262 - 4272. [Abstract] [Full Text] [PDF]

				M. Degen, F. Brellier, R. Kain, C. Ruiz, L. Terracciano, G. Orend, and R. Chiquet-Ehrismann Tenascin-W Is a Novel Marker for Activated Tumor Stroma in Low-grade Human Breast Cancer and Influences Cell Behavior Cancer Res., October 1, 2007; 67(19): 9169 - 9179. [Abstract] [Full Text] [PDF]

				M. Jinushi and G. Dranoff Triggering Tumor Immunity through Angiogenesis Targeting Clin. Cancer Res., July 1, 2007; 13(13): 3762 - 3764. [Full Text] [PDF]

				A. Perez-Diez, N. T. Joncker, K. Choi, W. F. N. Chan, C. C. Anderson, O. Lantz, and P. Matzinger CD4 cells can be more efficient at tumor rejection than CD8 cells Blood, June 15, 2007; 109(12): 5346 - 5354. [Abstract] [Full Text] [PDF]