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Abstract

Grant Number:	2R44CA083156-03
PI Name:	SOBOL, ROBERT E.
PI Email:	rsobol@magnum-rx.com
PI Title:
Project Title:	Complementary Adenoviral Vectors for Treatment of Cancer

Abstract: DESCRIPTION (provided by applicant) The major goal of this proposal is to determine the therapeutic potential of a replication conditional adenovirus vector, DuaI-AdlL-3. This vector system is composed of two transcomplementing adenoviruses that permit selective replication in the prostate and prostate tumors. It is designed to engender a multimodal therapeutic response by establishing a lytic infection in prostate tumor cells by enhancing the tumoricidal effects of radiation therapy and by enhancing the immune response to endogenous tumor antigens. The genome of one of the viral components, Max-AdlL-3, contains the adenoviral-inverted terminal repeats for replication, the adenoviral packaging signal, the E1 genes with E1A under the control of a prostate specific antigen (PSA) promoter, and an IL-3 expression cassette. This vector propagates only in cells that express PSA when the helper adenoviral vector is also present. In animal tumor models, the combination of IL-3 cytokine gene therapy with radiotherapy was synergistic, resulting in enhanced efficacy of local radiotherapy and systemic anti-tumor immunity. In the preclinical studies of the Phase I SBIR grant we have shown our DuaI-AdlL-3 oncolytic vector system exhibits the oncolytic, immunity enhancing, and radiation-enhancing properties incorporated into the vector. This Phase II proposal will extend this project to clinical application.

Thesaurus Terms:
Adenoviridae, interleukin 3, neoplasm /cancer immunotherapy, prostate neoplasm, technology /technique development, transfection /expression vector
alpha fetoprotein, clinical trial phase I, cytokine, gene expression, gene therapy, human therapy evaluation, prostate specific antigen, prostate surgery, radiosensitizer, tumor antigen, virus replication
Macaca fascicularis, clinical research, histopathology, human subject, laboratory mouse, patient oriented research, polymerase chain reaction

Institution:	MAGNUM THERAPEUTICS
	8395 CAMINO SANTA FE, STE B
	SAN DIEGO, CA 92121
Fiscal Year:	2003
Department:
Project Start:	07-MAR-2000
Project End:	31-AUG-2006
ICD:	NATIONAL CANCER INSTITUTE
IRG:	ZCA1

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