The Journal of Experimental Medicine
Cytokines Montreal 2008
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Published 15 March 2004. doi:10.1084/jem.20031190
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 6, 753-761
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Immunoprevention of Basal Cell Carcinomas with Recombinant Hedgehog-interacting Protein

Annika Vogt1, Pao-Tien Chuang2, Jennifer Hebert1, Jimmy Hwang3, Ying Lu3, Levy Kopelovich4, Mohammad Athar5, David R. Bickers5, and Ervin H. Epstein, Jr.1,3

1 Department of Dermatology, 2 Cardiovascular Research Institute and Department of Biochemistry and Biophysics, and 3 UCSF Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143
4 Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892
5 Department of Dermatology, Columbia University, New York, NY 10032

Address correspondence to Ervin Epstein, Jr., University of California San Francisco, San Francisco General Hospital, 1001 Potrero Ave., Bldg. 100-Rm. 269, San Francisco, CA 94110. Phone: (415) 647-3992; Fax: (415) 647-3996; email: epsteine{at}derm.ucsf.edu

Basal cell carcinomas (BCCs) are driven by abnormal hedgehog signaling and highly overexpress several hedgehog target genes. We report here our use of one of these target genes, hedgehog-interacting protein (Hip1), as a tumor-associated antigen for immunoprevention of BCCs in Ptch1+/- mice treated with ionizing radiation. Hip1 mRNA is expressed in adult mouse tissues at levels considerably lower than those in BCCs. Immunization with either of two large recombinant Hip1 polypeptides was well tolerated in Ptch1+/- mice, induced B and T cell responses detectable by enzyme-linked immunosorbent assay, Western blot, delayed type hypersensitivity, and enzyme-linked immunospot assay, and reduced the number of BCCs by 42% (P < 0.001) and 32% (P < 0.01), respectively. We conclude that immunization with proteins specifically up-regulated by hedgehog signaling may hold promise as a preventive option for patients such as those with the basal cell nevus syndrome who are destined to develop large numbers of BCCs.

Key Words: basal cell nevus syndrome • patched • skin cancer • immunization • mouse

Abbreviations used in this paper: BCC, basal cell carcinoma; BCNS, basal cell nevus syndrome; DTH, delayed-type hypersensitivity; Hip1, hedgehog-interacting protein; IR, ionizing radiation; ODN, oligodeoxynucleotides; TAA, tumor-associated antigen.


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