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Vector Prime/Protein Boost Vaccine That Overcomes Defects Acquired during Aging and Cancer¹

Yucheng Tang^2,*, Hakan Akbulut^*, Jonathan Maynard^2,*, Line Petersen^*, Xiangming Fang, Wei-Wei Zhang, Xiaoqin Xia^*, James Koziol, Phyllis-Jean Linton^* and Albert Deisseroth^3,*

^* Sidney Kimmel Cancer Center, and GenWay Biotech, Inc., San Diego, CA 92121, and The Scripps Research Institute, La Jolla, CA 92037

We showed that the Ad-sig-TAA/ecdCD40L vaccine induces a tumor suppressive immune response to the hMUC-1 and rH2N tumor-associated self Ags (TAA) and to the Annexin A1 tumor vascular Ag, even in mice in which anergy exists to these Ags. When the TAA/ecdCD40L protein is given s.c. as a boost following the Ad-sig-TAA/ecdCD40L vector, the levels of the TAA-specific CD8 T cells and Abs increase dramatically over that seen with vector alone, in young (2-mo-old) as well as old (18-mo-old) mice. The Abs induced against hMUC-1 react with human breast cancer. This vaccine also induces a 4-fold decrement of negative regulatory CD4CD25FOXP3-T cells in the tumor tissue of 18-mo-old mice. These results suggest that the Ad-sig-TAA/ecdCD40L vector prime-TAA/ecdCD40L protein boost vaccine platform may be valuable in reducing postsurgery recurrence in a variety of epithelial neoplasms.

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 This work was supported by the Breast Cancer Research Foundation, the Department of Defense Breast Cancer Research Program (DAMD 17-99-9457, DAMD 18-99-9477, and BC022063), and National Institutes of Health Grant SBIR 2003-2. Support was also received from the Kimmel Foundation, the Anthony Dewitt Frost Foundation, and the George and the Barbara Bush Leukemia Research Fund.

² Y.T. and H.A. are co-first authors.

³ Address correspondence and reprint requests to Dr. Albert Deisseroth, Sidney Kimmel Cancer Center, 10835 Road to the Cure, San Diego, CA 92121. E-mail address: adeisseroth{at}skcc.org

⁴ Abbreviations used in this paper: TAA, tumor-associated Ag; DC, dendritic cell; ecd, extracellular domain; AnxA1, Annexin A1; MMC, mitomycin C.