MONOCLONAL ANTIBODY-BASED THERAPY OF PROSTATE CNCER

DESCRIPTION: This proposal will investigate the use of Pro1.5, a monoclonal antibody to the novel human prostate antigen PCTA-1, as a potential immunotherapeutic agent for the treatment of human prostate cancer. The PCTA- 1 antigen is a member of the S-type lectin (i.e., galectin) family, other members of which are involved in cell-cell adhesion, extravasation, and metastatic spread. PCTA-1 appears to be specific for primary and metastatic prostate carcinoma and prostate intraepithelial neoplasia (PIN), but is not expressed by either normal prostate tissue or benign prostate hypertrophy (BPH). In preliminary studies, the PCTA-1-specific monoclonal antibody, Pro 1.5, has been shown to induce regression and complete remission of a well- established human prostate cancer line grown as xenografts in athymic nude mice. This proposal will attempt to 1) validate the utility of the Pro 1.5 monoclonal antibody as a therapeutic agent for treating prostate cancer, and 2) define the mechanism of action for the biological effects of this antibody. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 214 --PROJECT NUMBER......1 R43 CA76807-01 INVESTIGATOR NAME/ADDRESS FY 97 VOGELSONG, THOMAS L IRG/INTRAMURAL UNIT..ZRG7 INFIMED, INC AWARD AMOUNT......... $100,000 121 METROPOLITAN DRIVE LIVERPOOL, NY 13088 PERFORMING ORGANIZATION: INFIMED, INC. TITLE IMPROVED DETECTOR FOR ELECTRONIC PORTAL IMAGING ABSTRACT: "Visualization of low contrast anatomy and small implanted reference marker "seeds" in electronic portal imaging will dramatically improved by eliminating the noise effects of scattered radiation "direct hits", and achieving the high signal to noise ratio inherent in CCD sensors. A high- performance portal imaging system will be a key factor in reducing localization problems, thereby contributing to lower recurrence of tumors at the margins of the treatment field. An imaging system will be assembled using high density metal-phosphor converter as the sensor and a CCD for read out. The CCD will provide signal-to-noise rations 3-5 times greater than possible with video tubes at a much lower cost than flat panels. We will perform tests to demonstrate spatial resolution, signal- to-noise ratio, and detective quantum efficiency benefits in comparison to that of conventional systems based on metal/phosphor and electron beam video tube technology." $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 215 --PROJECT NUMBER......1 R43 CA76811-01 INVESTIGATOR NAME/ADDRESS FY 97 STEIN, JEFFREY L IRG/INTRAMURAL UNIT..ZRG5 RECOMBINANT BIOCATALYSIS, INC AWARD AMOUNT......... $95,679 10665 SORRENTO VALLEY ROAD SAN DIEGO, CA 92121 PERFORMING ORGANIZATION: DIVERSA CORPORATION TITLE RECOMBINANT EXPRESSION OF SMALL MOLECULE PATHWAYS ABSTRACT: This Phase I project will develop a recombinant system to stably clone and express multigene pathways encoding bioactive compounds. Due to the proliferation of antibiotic resistant strains of microbial pathogens and to demographic shifts the need for novel antibiotics, anticancer agents and other compounds greatly exceeds the present discovery rate despite recent increases in the screening efforts and the development of combinatorial techniques. A vast repository of pathways encoding potentially useful bioactive compounds resides within the uncultivated fraction of naturally occurring microbes; however, approaches to date have not successfully accessed this resource. As a first stem towards this goal, in Phase l a shuttle vector system will be developed based on an F factor replicon for stable propagation of clones in E coli and containing genes/sites for replication or integration in Streptomyces to express pathways encoding known polyketide antibiotics. In Phase II, these vectors will be used to construct "environmental libraries" containing the collective genomes of uncultivated microbes captured in substrate-doped traps designed to attract actinomycetes and other microbes likely to produce novel bioactive compounds.