Daniel A. Vallera, Ph.D. Professor Department of Therapeutic Radiology Ohio State University, 1978, Ph.D. valle001@umn.edu 612-626-6664 office 612-626-4323 lab

Research Interests:

Transplantation, cancer, leukemia, molecular therapeutics, gene therapy

Our laboratory specializes in the design and development of new anti-cancer biologic agents with the goal of getting them into the clinic as quickly as possible. Typically, new hybrid proteins are synthesized by combining genes encoding cancer cell binding domains with genes encoding molecules that deliver death signals. The resulting proteins selectively bind to cancer cells, internalize the death signal, and kill the cancer cells. Thus, they provide cancer specific therapy in a manner that chemotherapeutic agents cannot. These new anti-cancer agents are primarily directed to overexpressed signal markers on the surface of cancer cells and we have successfully produced promising fusion proteins that can kill brain tumors, breast cancer, leukemia, and cells causing organ rejection. In order to facilitate the delivery of these agents at the site of the tumor, another approach under study uses gene therapy. We are fashioning retroviruses containing our target genes and using them to infect tumor reactive T cells. The T cells have the ability to migrate to tumor and secrete the anti-cancer molecule at site where they can have the greatest effect. Another facet of our work focuses on the use of targeting powerful beta irradiation-emitting radionuclides, to cancer cells. Certain isotopes can be conjugated to cancer cell binding antibodies in such a way that they can selectively bind to tumors and cause their regression. In this instance, internalization of these molecules into cells are unnecessary. The cross-fire effect is potent enough to destroy even large tumors and the side effects seem tolerable. Through the design and production of these new molecules we hope to not only devise urgently needed alternative cancer therapies, but to further our understanding of the intricacies of protein engineering.

Selected Recent Publications:

• Vallera DA, Jin N, Yanqun S, Panoskaltsis-Mortari A, Kelekar A, and Chen W. Retroviral immunotoxin gene therapy of leukemia in mice using leukemia-specific T cells transduced with an IL-3/Bax fusion protein gene Human Gene Therapy 14:1787-1798, 2003

• Li C, Hall WA, Jin N, Todhunter DA, Panoskaltsis-Mortari A, Vallera DA. Targeting glioblastoma multiforme with an IL-13/diphtheria toxin fusion protein in vitro and in vivo in nude mice. Protein Eng. 2002 May;15(5):419-427.

• Vallera DA, Li C, Jin N, Panoskaltsis-Mortari A, Hall WA. Targeting urokinase-type plasminogen activator receptor on human glioblastoma tumors with diphtheria toxin fusion protein DTAT. J Natl Cancer Inst. 2002 Apr 17;94(8):597-606.

• Jin N, Chen W, Blazar BR, Ramakrishnan S, Vallera DA. Gene therapy of murine solid tumors with T cells transduced with a retroviral vascular endothelial growth factor--immunotoxin target gene. Hum Gene Ther. 2002 Mar 1;13(4):497-508. pdf

• Vallera DA. Gene therapy with immunotoxins. Methods Mol Biol. 2001;166:235-46. Review

.Last modified on December 5, 2003.