Abstract
Mice were immunized with live breast cancer cells or fresh breast cancer membrane extract. The immune splenocytes were fused with SP2/0 myeloma cells and the hybridomas were screened for breast cancer reactive antibody production. Over 100 monoclonal antibodies were purified and characterized. Antibodies were found which bound only a few substructures in normal tissues and which bound the majority of breast cancers. These antibodies were infrequent. A number of these antibodies fall into groups recognizing determinants on several distinct surface or intracellular proteins and cross-react most with endometrial, prostate and ovarian cancer. These antibodies were conjugated to ricin toxin A chain (RTA) and a fraction of these RTA conjugates were able to selectively kill tumor cells in vitro (i.e. low TCID50 on tumor cells but high TCID50 on fibroblasts). Antibodies with higher affinity and antigen copy number produced more active conjugates. Some RTA antibody conjugates showed moderate tumor growth inhibitory activity in vivo at LD10. The poor therapeutic index in vivo may be due to rapid clearance of the conjugate from the plasma to the liver and other organs which results in poor tumor localization of conjugate.
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© 1985 Martinus Nijhoff Publishing, Boston
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Frankel, A. et al. (1985). Breast Cancer Immunotoxins. In: Ceriani, R.L. (eds) Monoclonal Antibodies and Breast Cancer. Developments in Oncology, vol 35. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2617-5_19
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DOI: https://doi.org/10.1007/978-1-4613-2617-5_19
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