Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 99.99K | Year: 1996
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 99.97K | Year: 1997
PSMA is a prostate-specific membrane bound protein antigen which is defined by the murine monoclonal antibody 7E11.C5. PSMA is highly expressed in prostatic carcinomas, particularly in the more resistant and aggressive clones of cells which appear as the disease progresses. The 7E11.C5 antibody has been successfully applied to immunoscintigraphy to aid in the localizing of metastatic disease. Because of the high tissue specificity of this antigen and the existence of appropriate monoclonal antibodies, the proposed experiments are intended to test the potential of immunotoxin therapy as a means for controlling the disease. Experiments will utilize both tissue culture systems and animal models to assess the potential of this modality to be expanded upon in future research. These experiments will test cell killing by immunotoxin in expressing and non-expressing human prostate cell lines. Based on these results, immunotoxin challenge of INCaP cells inoculated into nude mice will be tested, along with an analysis of the effect of immunotoxin administration on growing INCaP tumors in nude mice. The results of these experiments will provide definitive evidence relating to the future value of immunotoxin use based on the PSMA antigen for prostate cancer treatment in a clinical setting.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 97.05K | Year: 1995
This project is designed to assess the feasibility of producing for commercial application. Severalserine/threonine (ser/thr) protein phosphatases which demonstrate specificity towards specific typesOne particular extract has already been demonstrated to have activity which inhibits only type 1 prodate, five ser/thr protein phosphatase types have been biochemically identified and they are known tphysiological regulation of a variety of biological phenomena ranging from gene transcription to celcontraction. Currently the only known inhibitors of these phosphatases are non-specific, either inhiprotein phosphatases or inhibiting other enzymes as well (i.e. protein kinases). In the ser/thr protwe propose to purify are potentially vastly superior to current inhibitors because their activity isphosphatase. Several extracts containing inhibitors of AP-1 mediated gene transcription have been idtranscription through AP-1 is known to involve the fos/jun proto oncogenes and to be associated withcarcinogenesis. The inhibitors of transcriptional activation have application for the research commutherapeutic use for proliferative diseases.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 99.25K | Year: 1995
Characteristic base lesion profiles from hydroxyl-radical induced oxidative damage occur in DNA frobreast tissue compared to DNA from invasive ductal carcinomas or histologically normal breast tissuepatients. These profiles shift from predominantly non-mutagenic lesions in non-cancer tissues to muttissues, regulated, most probably, the cellular redox potential. Evidence indicates the nature of DNpredictive of future breast cancer risk. These lesions are quantifiable using gas-chromatography-masHPLC analyses on isolated and derivatized DNAs. The objective is to develop DNA base lesion-specificantibodies to establish a quantitative immunoassay. Such an assay would provide a reliable quantitacost technology with critical importance in future clinical applications. Base lesion haptens will bcarrier protein for immunization in mice. Hybridomas will be screened for lesion specificity, bindiantigen binding response. Initial characterization of antibodies will involve analysis of hapten cophysiological DNA specimens of known base lesion concentration as determined by standard gas-chromatspectrometric determinations. Based upon these results, antibodies will be selected for their suitadevelopment of immunoassays.