The overall objective of this project is to devise and test various modes and combinations of antibody-mediated isotopic therapy of cancer. The experimental model to be used is the carcinoembryonic antigen (CEA) and colon-specific antigen-p (CSAp) producing GW-39 human colonic carcinoma xenografted in hamsters. The therapeutic efficacy of 131-I, 64-Cu, and 32-P labeled affinity-purified, goat antibodies against CEA and CSAp will be compared with that of murine monoclonal antibodies directed against these two tumor markers. Monoclonal antibodies with different epitope specificity and affinityas well as defined mixtures of these antibodies against different epitopes on the same antigen or against different antigens will be examined for therapeutic advantage. Saturation and binding characteristics of monoclonal antibodies to GW-39 tumors will be compared to that of goat antibodies. The radioactive antibodies, either intact or fragments thereof, will be used in different dose and treatment schedules to affect the growth behavior of GW-39 tumors in order to determine the optimal conditions for therapy. The relationship of tumor size at the onset of therapy to therapeutic effectiveness also will be evaluated. The results of these studies will provide an understanding of the relative therapeutic advantage of hybridoma-derived monoclonal antibodies over conventional antibody preparations, and a definition of monoclonal antibody characteristics that influence their efficacy as isotopic therapeutic agents for eventual use in cancer patients.
| Sharkey, R M; Kaltovich, F A; Shih, L B et al. (1988) Radioimmunotherapy of human colonic cancer xenografts with 90Y labeled monoclonal antibodies to carcinoembryonic antigen. Cancer Res 48:3270-5 |
| Sharkey, R M; Primus, F J; Shochat, D et al. (1988) Comparison of tumor targeting of mouse monoclonal and goat polyclonal antibodies to carcinoembryonic antigen in the GW-39 human tumor-hamster host model. Cancer Res 48:1823-8 |
| Sharkey, R M; Primus, F J; Goldenberg, D M (1987) Antibody protein dose and radioimmunodetection of GW-39 human colon tumor xenografts. Int J Cancer 39:611-7 |
| Sharkey, R M; Pykett, M J; Siegel, J A et al. (1987) Radioimmunotherapy of the GW-39 human colonic tumor xenograft with 131I-labeled murine monoclonal antibody to carcinoembryonic antigen. Cancer Res 47:5672-7 |
