Concepts in the delivery of monoclonal antibodies in the targeting of human carcinomas

Abstract

We have previously reported a high degree of selective binding of monoclonal antibody (MAb) B72.3 to a wide range of carcinoma versus normal tissues. While the diagnostic targeting of a primary or metastatic carcinoma lesion with a MAb is an end unto itself, it should also be considered as a first step toward the use of the MAb in tumor therapy. As we proceed with the use of MAbs in therapeutic applications, we are concomitantly characterizing the MAbs and associated tumor antigens to better understand their composition and nature ultimately in order to be able to manipulate their interaction. In this article we will discuss the use of MAbs in several aspects of clinical oncology, including tumor targeting clinical studies using MAb B72.3. These studies also include the regulation of tumor antigenic expression using preclinical models. We will present data on the use of a biological response modifier, recombinant human leukocyte (alpha) interferon (rHu-IFN-α), to amplify antigenic expression in carcinoma cells. We will discuss the use of MAb B72.3 in the localization of metastatic lesions in colorectal cancer patients, the findings of simultaneously administered B72.3 (i.v. and i.p.), and the pharmacokinetics associated with MAb administration. Finally, we will discuss the potential clinical uses of genetically engineered recombinant/chimeric MAbs, MAbs conjugated to toxins, drugs and/or radionuclides, MAb combinations, and second generation MAbs of predefined specificity.