Martin V. Haspel

Development and Characterization of Human Monoclonal Antibodies and Their Application in the Radioimmunodetection of Colon Carcinoma

Significant progress has been made in the application of monoclonal antibody technology to clinical diagnosis of cancer and to management of the disease. Antibodies labeled with radioactive isotopes have been demonstrated to localize in tumors of the gastrointestinal tract (1–6), ovary (6), breast (6,7), and skin (8) and promise to be very helpful in identifying metastases in patients with these tumors. However, there remain several problems to be resolved before radiolabeled antibody detection of tumor foci will be applied as an accepted and routine diagnostic/prognostic procedure. Problems include antibody cross-reactivity with normal tissues (5,6,9,10), low level penetration of antibody into tumor tissue (5,9,10), and inhibitory effects of specific circulating antigen (11). Current research is focused on selecting antibodies with the most desirable characteristics for tumor detection, improving chemistries to allow use of more appropriate radionuclides, and defining the effective clinical applications with regard to the tumor types, tumor sites and available diagnostic equipment and procedures.

Selection of Growth Factors and Myelomas To Enhance Monoclonal Antibody-Producing Hybridoma Formation

The potential uses of monoclonal antibodies (Mab) encompass diverse areas in the fields of biology and chemistry, i.e., detecting microbial contamination in food products (1), purifying substances from complex mixtures (2), and identifying and eradicating human cancerous cells (3-5). These are just a few of the reasons substantial work has been directed toward optimizing conditions for production of stable Mab-secreting hybridomas since the first successes in this area were reported in 1975 by Kohler and Milstein (6). Their strategy for producing continuous lines of specific immunoglobulin-producing B-lymphocytes was to fuse them with a myeloma tumor cell. This has been accomplished with immune B-cells from mice, rats (7), and humans (3) fused with myelomas primarily from mice. The specific problems encountered after such a fusion are (1) selection of hybrid cells from nonfused lymphocytes and myelomas, (2) clonal growth hybrids to assure the monoclonality of the antibody being produced, and (3) long term of growth of specific antibody-producing cells. The purpose of this article is to present various means of overcoming these three basic problems. The first of these problems has been dealt with by developing myelomas that are enzyme deficient and can be removed selectively from hybridomas with defined culture medium.