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Research Institute

Prem Seth, PhD

Prem Seth, PhDDepartment of Medicine
Director, Gene Therapy Program

Contact information
847.570.2378
pseth@northshore.org

Research Interests

Novel Gene Therapeutic Strategies for Targeting Cancer:
The majority of patients with advanced breast and prostate cancers will develop bone metastasis resulting in bone destruction. Our laboratory is developing a therapeutic approach that will destroy the primary tumors, and simultaneously inhibit the bone metastasis associated with these cancers. We plan to learn whether a strategy which combines the oncolytic effects of an adenoviral vector with selective expression of soluble form of TGFß receptor II (sTGFßRII) offers a therapeutic advantage. We chose to target the TGFß pathway because high levels of TGFß protein enhance tumor invasion, bone metastasis. There are two types of functional TGFß receptors - ßRI, and ßRII. Inactivating TGFßRII function can inhibit TGFß-mediated signal transduction lending support to the model that the inhibition of TGFß function by sTßRII can inhibit bone metastasis. In the recent years, replicating oncolytic adenoviral vectors have shown promise as effective anti-tumor agents. However, their potential to control bone metastasis has not yet been explored  Using an oncolytic adenoviral vector expressing sTGFßRII, we are testing  the hypothesis that the viral  backbone will be oncolytic to the tumor cells, and the vector-mediated production of sTGFßRII and secretion into the blood will block the effects of TGFß, together inhibiting metastatic potential of cancer cells.

Professional Memberships/Affiliations/Activities

  • American Association for Cancer Research
  • The American Society of Gene Therapy
  • International Society of Cancer Gene Therapy
  • American Society of Biochemistry and Molecular Biology
  • Member Editorial Board, Cancer Gene Therapy (1999-current)
  • Member Editorial Board, Cancer Biology and Therapy (1999-current)
  • Member Editorial Board, Human Gene Therapy (2003-current)
  • Abstract reviewer for American Society of Gene Therapy (2000-2005)
  • American Cancer Society (Molecular Genetics and Oncogenes study section: Permanent member 2001- 2005)
  • National Institutes of Health (Proteomics, Protein expression and Protein therapeutics special study section: ad hoc committee member), 07/2000, 10/2000, 02/2001, 07/2001, 10/2001, 02/2002, 06/2002, 10/2002, 07/2003
  • National Cancer Institute, Flexible System to Advance Innovative Research for Cancer Drug Discovery, Ad hoc member, 03/2004
  • American Cancer Society - Member, Site Visit Team, SALK Institute, La Jolla, CA, 10/2005
  • National Cancer Institute Ad hoc member Developmental Therapeutics study section- 10/2005, 03/2006, 06/2006, 02/2007, 05/2007, 9/2007, 01/2008
  • Alliance for Cancer Gene Therapy -Grant reviews committee member- 04/2006, 06/2006
  • National Cancer Institute, - Ad hoc member, Special Emphasis Panel/Scientific Review Group ZRG1 ONC-F (02) (M) 05/2006
  • National Cancer Institute, - Ad hoc member, Special Emphasis Panel/Scientific Review Group ZRG1 ONC-K (02) (M) 02/2008
  • Moderator-Cancer Gene Therapy Replacement Session, American Society of Gene Therapy, June, Seattle, 2001
  • Committee Member (Cancer Gene Therapy), American Society of Gene Therapy Conference, 2000-2004
  • Moderator-Educational Session on Cell cycle/Apoptosis, American Society of Gene Therapy Conference, Denver, June 2000
  • Chairman, Cancer Gene Therapy conference, Redwood city, CA, April 1999, London, June 1999-2002, Mumbai Nov. 2007

Scholarly Work

Publications in Peer-Review Journals:

  1. Akhtari, M., Mansuri, J., Newman, K., Guise, T., Seth, P.  Biology of Breast Cancer Bone Metastasis. (2008) Cancer Biol Ther 7:3-9.
  2. Seth, P., Wang, Z-G., Pister, A., Zafar, MB., Sung, K., Guise, T., Wakefield, T. (2006) Development of Oncolytic Adenovirus Armed with a Fusion of Soluble Transforming Growth Factor-beta Receptor II and Human Immunoglobulin Fc for Breast Cancer Therapy. Hum Gene Ther. 17:1152-1160.
  3. Wang, Z., Zhao, W., Ramachandra, M., Seth, P. (2006)  An Oncolytic Adenovirus Expressing Soluble TGF-ß Type II Receptor for Targeting Breast Cancer : In Vitro Evaluation. Mol Cancer Ther. Mol Cancer Ther. 5:367-373.
  4. Mitrofanova E., Unfer R., Vahanian N., Daniels W., Roberson E., Seregina T., Seth P., Link C Jr. (2004)  Rat sodium iodide symporter for radioiodide therapy of cancer. Clin Cancer Res 10:6969-76.
  5. Turturro, F., Seth, P. (2003)  Prolonged adenovirus-mediated expression of p27 kip1 unveils unexpected effects of this protein on the phenotype of SUDHL-1 4 cells derived from t(2;5)-anaplastic large cell lymphoma. Leukemia Res 1596:1-7.
  6. Turturro, F., Arnold, M. D., Frist, A. Y., Seth, P. (2002)  Effects of adenovirus-mediated expression of p27Kip1, p21Waf1 and p16INK4A in cell lines derived from t(2;5) anaplastic large cell lymphoma and Hodgkin's disease. Leuk Lymphoma 43:1323-1328.
  7. Habib, N., Salama, H., Abd, E. L., Abu, M. A., Isac Anis, I., Abd Al Aziz, R. A., Sarraf, C., Mitry, R., Havlik, R., Seth, P., Hartwigsen, J., Bhushan, R., Nicholls, J., Jensen, S. (2002) Clinical trial of E1B-deleted adenovirus (dl1520) gene therapy for hepatocellular carcinoma. Cancer Gene Ther 9:254-259.
  8. Turturro, F., Frist, A. Y., Arnold, M. D., Seth, P. (2002)  Effects of adenovirus expressing p27/Kip1, p21/Waf1 and p16/INK4A in cell lines derived from t(2;5) anaplastic large cell lymphomas and Hodgkins Disease. Leukemia and Lymphoma 43:1323-1328.
  9. Zhao, W., Kobayashi, M., Ding, W., Yuan, L., Seth, P., Cornain, S., Wang, J., Okada, F., Hosokawa, M.  Suppression of in vivo tumorigenicity of rat hepatoma cell line KDH-8 cells by soluble TGF-beta receptor type II. Cancer Immunol Immunother 2002, 51:381-8.
  10. Higginbotham, J. N., Seth, P., Blaese, R. M., Ramsey, W. J. (2002)  The release of inflammatory cytokines from human peripheral blood mononuclear cells in vitro following exposure to adenovirus variants and capsid. Hum Gene Ther 13:129-141.
  11. Jacob, T., Ascher, E., Higorani, A., Gunduz, Y., Yorkovich, W., Seth, P. (2001).  Von-Hippel-Lindau gene therapy: a novel strategy in limiting endothelial cell proliferative activity. Ann Vasc Surg 15:1-6.
  12. Turturro, F, Frist, A. Y., Arnold, M. D., Pal, A., Cook, G. A., Seth, P. (2001)  Comparison of the effects of recombinant adenovirus-mediated expression of wild type p53 and p27/Kip1 on cell cycle and apoptosis in SUDHL-1 cells derived from anaplastic large cell lymphoma. Leukemia 15:1225-12231.
  13. Turturro, F., Frist, A. Y., Arnold, M. D., Seth, P., Pulford, K. (2001)  Biochemical differens between SUDHL-1 and KARPAS 299 cells derived from t (2; 5)-positive anaplastic large cell lymphomas are responsible for the difference sensitivity to the anti proliferative effect of p27 (Kip1). Oncogene 20:4466-4475.
  14. Seth, P. Adenoviral vectors (2000). Adv Exp Med Biol 465:13-22.
  15. Katayose, D. and Seth, P. (1999).  Development of Adenoviral vectors for gene therapy. In: Adenoviruses: Basic Biology to Gene Therapy (P. Seth ed). R. G. Landes Company, Austin, TX, pp 91-101.
  16. Rakkar, A, Li, Z., Katayose, Y., Kim, M., Cowan, K. H., and Seth, P. (1998)  Adenoviral expression of the cyclin-dependent kinase inhibitor p27/Kip1: A strategy for breast cancer gene therapy. J. Natl. Cancer Institute.  90:1836-1838.
  17. Li, Z., Rakkar, A., Katayose, Y., Kim, M., Shanmugam, N., Moul, J. W., McLeod, D. G., Cowan, K. H., and Seth, P. (1998)  Efficacy of multiple administrations of a recombinant adenovirus expressing wild type p53 in an immune-competent mouse tumor model. Gene Ther. 5:605-613.

Books:

  1. Book Editor: Seth, P. (1999). Adenoviruses: Basic Biology to Gene Therapy (editor P. Seth). R. G. Landes company, Austin, TX, pp. 1-314.