Version 2.1.1.0

Abstract

Grant Number:	1R43CA099891-01
PI Name:	LIN, AUGUSTINE Y.
PI Email:	alin@mithragen.com
PI Title:
Project Title:	Dendritic Cell-Mediated Prostate Cancer Immunotherapy

Abstract: DESCRIPTION (provided by applicant): In American and European men, prostate cancer is the most commonly diagnosed form of cancer and is second only to lung cancer as the leading cause of cancer-related death. In 2001 alone, there were 198,000 new diagnoses and 31,500 deaths in the United States. While detection and diagnosis have markedly improved since the advent of routine PSA screening, there have been no major improvements in treatment regimens nor changes in mortality since the introduction of androgen therapy in the 1940's. This Phase I proposal seeks to initiate the development of an efficacious and cost-effective DNA vaccine by using a proprietary technology that allows tumor-associated antigens (TAAs) to be presented directly to dendritic cells, activating CD8+ cytotoxic T-lymphocyte (CTL) responses, antibody responses, and, most-importantly, a robust CD4+ helper T-cell (Th) response. CD4+ helper T-cells aid in the brchestration of the immune response and play a key role in the formulation of immunological memory; thus, the elicitation of a CD4+ response should result in a vaccine product which is both efficacious and cost-effective when used in conjunction with a DNA-based delivery platform. PSMA (prostate-specific membrane antigen) is a TAA with an expression pattern limited almost exclusively to the prostate and is known to be up-regulated in metastatic disease. Phase I SBIR research will demonstrate proof of principle by incorporating the PSMA TAA into the proprietary vaccine construct and characterizing antibody, CD4+-specific Th, and CD8+-specific CTL responses in immunized C57BL/6 mice. Additionally, a tumor challenge study will be performed to demonstrate the biological relevance of this immune response in vivo.

Thesaurus Terms:
antigen antibody reaction, dendritic cell, gene delivery system, neoplasm /cancer immunotherapy, neoplasm /cancer vaccine, prostate neoplasm, tumor antigen, vaccine development, vector vaccine
cytotoxic T lymphocyte, helper T lymphocyte, membrane protein
laboratory mouse

Institution:	MITHRAGEN, INC.
	8014 EL RIO
	HOUSTON, TX 77054
Fiscal Year:	2003
Department:
Project Start:	12-MAR-2003
Project End:	31-AUG-2003
ICD:	NATIONAL CANCER INSTITUTE
IRG:	ZRG1

---