The long term objective of this project is to develop a new modality for anti-tumor activity of chemotherapeutic agents for treatment of prostate tumor. To achieve this goal it is proposed to use a specific hybridoma-derived monoclonal antiprostatic acid phosphatase IgG1 (anti-PAP IgG1) antibody as carrier to deliver antitumor agents. Therefore, the specific aims of this investigation are (a) preparation of cytotoxic agent-anti-PAP IgG1 antibody conjugate; cytotoxic agents employed are 5-fluouracil deoxyriboside (Fudr), methotrexate and ricin A chain; (b) characterization of antibody activity in these conjugates; (c) evaluation of anti-tumor activities of these conjugates against human prostate tumor in vitro (cell culture) and in vivo (athymic nude mice). A specific F(ab')2 anti-PAP fragment will be isolated and purified from hyridoma monoclonal anti-PAP IgG1 antibody by ammonium sulfate precipitation, DEAE cellulose chromatography, immunoadsorbent chromatography, pepsin digestion and gel filtration. Anti-tumor agent will be linked to F(ab')2 anti-PAP fragments with bifunction coupling reagents and other established coupling procedures. The pharmacological and immunological reactivities of resulting conjugates will be characterized and evaluated against prostate tumor cells in vitro studies. The therapeutic effects, pharmacokinetics and disposition of these conjugates will be studied in athymic nude mice bearing human prostate tumor.
| Deguchi, T; Chu, T M; Leong, S S et al. (1987) Potential therapeutic effect of adriamycin-monoclonal anti-prostatic acid phosphatase antibody conjugate on human prostate tumor. J Urol 137:353-8 |
| Deguchi, T; Chu, T M; Leong, S S et al. (1986) Effect of methotrexate-monoclonal anti-prostatic acid phosphatase antibody conjugate on human prostate tumor. Cancer Res 46:3751-5 |
