Lewis M. Slater
Professor of Medicine & Pathology, Medicine
School of Medicine
School of Medicine
M.D., University of Vermont, 1962
University of California, Irvine
Department of Medicine
Med Surge II, Room 375B
Mail Code: 4060
Irvine, CA 92697
Department of Medicine
Med Surge II, Room 375B
Mail Code: 4060
Irvine, CA 92697
Research Interests
Cancer chemotherapy; tumor immunology; lung cancer; leukemia and lymphoma
Research Abstract
Dr. Slater's research relates to tumor immunology. He has focused on tumor cell modification and pharmacologic methods to promote tumor immunity.
Pharmacologic Induction of TUMOR Immunity:
Many attempts at induction of tumor immunity or stimulation of tumor rejection relate to molecular biologic methods. Pharmacologic approaches have been limited. Dr. Slater’s work relates to the pharmacologic induction of tumor immunity by VP-16 (Etoposide), a commonly used topoisomerase II inhibiting anti-neoplastic drug used to treat leukemia, lymphoma, germ cell tumors, and lung cancer. It focuses on the use of VP-16 for induction of tumor immunity in murine Lewis lung cancer (3LL). Many C57 Bl/6 mice successfully treated with VP-16 for 3LL, develop immunity to 3LL. Long surviving mice previously treated for 3LL with VP-16 also reject B-16 melanoma, an unrelated syngeneic tumor. Dr. Slater’s laboratory has also shown the feasibility of immunizing naïve C57 Bl/6 mice with viable 3LL tumor cells modified in vitro by VP-16.
Dr. Slater’s laboratories recent experiments show that VP-16 modified 3LL tumor cells (3LL/VP-16) overexpress heat shock protein 60, an important stimulator of innate immunity. In addition, 3LL/VP-16 cells display enhanced m RNA expression for TGF beta and TNF alpha, key cytokines involved in the growth and differentiation of dendritic cells. These observations may also explain non-specific tumor immunity relative to rejection of B-16 melanoma by mice successfully treated for lung cancer by VP-16.
It is generally accepted that chemotherapeutic effects in tumor reduction relate to first order kinetics and that cytotoxic chemotherapy cannot therefore completely eradicate all tumor cells to promote tumor cure. Dr. Slater’s work suggests that chemotherapeutic cure of neoplasia relates to combined direct tumor cytotoxity as well as tumor cell antigenetic modulation which in turn permits host immune recognition and subsequent tumor rejection. Its significance relates to the potential development of tumor vaccines and the use of VP-16 conditioned autologous tumor cells in adjuvant therapy of cancer.
Pharmacologic Induction of TUMOR Immunity:
Many attempts at induction of tumor immunity or stimulation of tumor rejection relate to molecular biologic methods. Pharmacologic approaches have been limited. Dr. Slater’s work relates to the pharmacologic induction of tumor immunity by VP-16 (Etoposide), a commonly used topoisomerase II inhibiting anti-neoplastic drug used to treat leukemia, lymphoma, germ cell tumors, and lung cancer. It focuses on the use of VP-16 for induction of tumor immunity in murine Lewis lung cancer (3LL). Many C57 Bl/6 mice successfully treated with VP-16 for 3LL, develop immunity to 3LL. Long surviving mice previously treated for 3LL with VP-16 also reject B-16 melanoma, an unrelated syngeneic tumor. Dr. Slater’s laboratory has also shown the feasibility of immunizing naïve C57 Bl/6 mice with viable 3LL tumor cells modified in vitro by VP-16.
Dr. Slater’s laboratories recent experiments show that VP-16 modified 3LL tumor cells (3LL/VP-16) overexpress heat shock protein 60, an important stimulator of innate immunity. In addition, 3LL/VP-16 cells display enhanced m RNA expression for TGF beta and TNF alpha, key cytokines involved in the growth and differentiation of dendritic cells. These observations may also explain non-specific tumor immunity relative to rejection of B-16 melanoma by mice successfully treated for lung cancer by VP-16.
It is generally accepted that chemotherapeutic effects in tumor reduction relate to first order kinetics and that cytotoxic chemotherapy cannot therefore completely eradicate all tumor cells to promote tumor cure. Dr. Slater’s work suggests that chemotherapeutic cure of neoplasia relates to combined direct tumor cytotoxity as well as tumor cell antigenetic modulation which in turn permits host immune recognition and subsequent tumor rejection. Its significance relates to the potential development of tumor vaccines and the use of VP-16 conditioned autologous tumor cells in adjuvant therapy of cancer.
Publications
Eilon GF, Weisenthal L, Stupecky M, Landucci G, Slater LM. Antineoplastic activity of
idazoxan hydrochloride. Cancer Chemotherapy and Pharmacology 64(6):1157-1163, 2009.
idazoxan hydrochloride. Cancer Chemotherapy and Pharmacology 64(6):1157-1163, 2009.
Slater LM, Stupecky M, Sweet P, Osann KE. Enhancement of leukemia rejection by mice successfully treated for L1210 leukemia due to low dose compared to high dose VP-16. Leukemia Research 26:203-206,2002
Slater LM, Stupecky M, Sweet P, Osann K, Eklof A, and Arquilla ER. Etoposide induction of tumor immunity in Lewis Lung cancer. Cancer Chemotherapy and Pharmacology 48:327-332,2001
Slater LM,Sweet P, Wetzel M, Stupecky M, and Osann K. Comparison of Cyclosporin A,Verapamil, PSC 833 and Cremophor EL as Enhancing Agents of VP-16 Murine Lymphoid Leukemias. Leukemic Research 19:543-548,1995
Slater, L.M., Wetzel, M., Cho, J., Sweet, P. Development of cyclosporin A mediated immunity in L1210 leukemia. Br. J. Cancer 64:1098-1102, 1991.
Slater, L.M., Sweet, P., Stupecky, M., Reynolds, J.T. Cyclosporin A/VP-16 produced immunity to L1210 leukemia: The participation of cytotoxic CD-8 T-lymphocytes. Clin. Immunol. Immunopath. 75:239-245, 1995
Professional Societies
American Association of Cancer Research; American Society of Clinical Oncology
American Society of Hematology
Link to this profile
https://faculty.uci.edu/profile/?facultyId=3014
https://faculty.uci.edu/profile/?facultyId=3014
Last updated
04/19/2010
04/19/2010