Martin J. Cannon

Professor Department of Microbiology & Immunology

Immunology/Virology

Research Interest:  Viral and tumor immunology

Ph.D. , University of London

Postdoctoral , MRC National Institute for Medical Research, London, and the Scripps Research Institute, La Jolla

Phone: (501) 296-1254

Fax: (501) 686-5459

E-mail

Research Description

Serine proteases as target antigens for dendritic cell immunotherapy for cancer
Our attention has focused on the proposal that tumor-associated proteases may represent attractive candidates as targets for immunotherapy. Serine proteases are involved in many biological functions of cancer cells, including invasion and metastasis, and activation of growth and angiogenic factors. Using redundant PCR primers to sequences comprising the most highly conserved regions of proteases, O'Brien and colleagues at UAMS sought novel protease genes that are differentially expressed in ovarian carcinomas. Several candidate tumor markers have been identified, including hepsin, stratum corneum chymotryptic enzyme (SCCE), protease M and the tumor-associated differentially-expressed gene (TADG)-12, TADG-14, TADG-15 (matriptase) and TADG-16 (testisin), all of which are serine proteases. These genes are highly expressed in ovarian carcinomas, but not in normal ovaries or most other normal tissues.

By virtue of their central role in tumor progression, many proteases are also expressed by epithelial malignancies other than ovarian cancer, and thus our research is not confined to one disease. For example, our own studies and independent gene array analyses have shown that both hepsin and TADG-15 (matriptase) are major prostate cancer antigens, being highly expressed in prostate tumors, but absent in benign prostatic hyperplasia or most normal tissues. Hepsin and TADG-15 expression levels also show a strong positive correlation with Gleason grade. We are investigating both antigens as targets for dendritic cell (DC) immunotherapy of prostate cancer.

References

Santin, A.D., Bellone, S., Palmieri, M., Ravaggi, A., Romani, C., Tassi, R., Roman, J.J., Burnett, A., Pecorelli, S., Cannon, M.J. 2006. HPV16/18 E7-pulsed dendritic cell vaccination in cervical cancer patients with recurrent disease refractory to standard treatment modalities. Gynecol. Oncol. 100:469-478.

Bondurant, K.L., Crew, M.D., Santin, A.D., O'Brien, T.J., Cannon, M.J. 2005. Definition of an immunodominant region within the ovarian tumor antigen stratum corneum chymotryptic enzyme. Clin. Cancer Res. 11:3446-3454.

Santin, A.D., Cane', S., Bellone, S., Palmieri, M., Siegel, E.R., Thomas, M., Roman, J.J., Burnett, A., Cannon, M.J., Pecorelli, S. 2005. Treatment of chemotherapy-resistant human ovarian cancer xenografts in C.B-17/SCID mice by intraperitoneal administration of Clostridium perfringens enterotoxin (CPE). Cancer Res. 65:4334-4342.

Cannon, M.J., Santin, A.D., O'Brien, T.J. 2004. Immunological treatment of ovarian cancer. Curr. Opin. Obstet. Gynecol. 16:87-92.

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