Tumor-specific Monoclonal Antibodies Research Articles

Radioimmunoimaging of human small cell lung carcinoma with I-131 tumor specific monoclonal antibody.

In this study, an IgM monoclonal antibody (MAb600D11) directed against human small cell lung cancer (NCI-H69) was radiolabeled with iodine-131, and the biodistribution and image quality of the radiolabeled antibody was evaluated. Radiolabeling was achieved in a solid-phase system consisting of 1,3,4,6-tetrachloro-3a,6a-diphenylglycoluril. Labeling efficiencies and protein purification were accomplished using gel exclusion chromatography while radioimmunoreactivity was determined using a solid-phase radioimmunoassay procedure. The biodistribution of I-131-labeled MAbs was determined in Sprague-Dawley rats up to 7 days after injection. Highest organ concentrations were observed in liver (3.91 +/- 0.47 (SD) and 0.17 +/- 0.04 (SD) mean percent injected dose at 1-7 days after injections) and in thyroid (5.33 +/- 0.71 (SD) and 5.32 +/- 2.01 (SD) mean percent injected dose at 1-7 days after injection). Nude mice, bearing either a small cell lung tumor (NCI-H69) or a nonspecific tumor (adenocarcinoma), were injected with 400-800 microCi of I-131 labeled monoclonal antibody. Optimum tumor visualization was observed 2-4 days after injection with tumor concentrations as high as 10.4% of the initial injected dose. The results demonstrated that radioimmunoimaging of human small cell lung carcinoma was feasible with the tumor-specific IgM I-131-labeled MAb.

Tumor-Specific Monoclonal Antibodies for Renal Cell Carcinoma

Monoclonal antibodies, tumor-specific for renal cell carcinoma (RCC), were produced in Balb/C mice, hyperimmunized with tumor cell suspensions from a histological grade II tumor. Boosting with lectin-immobilized tumor-antigen rendered high yields of specific antibody-producing hybrids. Hybridoma supernatants were screened for specificity using a solid-phase enzyme-linked immunoassay. Testing in parallel for reactivity with tumor tissue and corresponding autologous normal kidney material, only those hybrids producing antibodies exclusively reactive with RCC were propagated, resulting in 4 stable, highly productive subclones. Using the immunoperoxidase staining technique, tissue sections from 97 different RCC specimens and corresponding normal kidneys were evaluated for reactivity with the monoclonal antibodies. Over 90% of RCC were strongly positive, whereas normal kidney tissue did not react. Other normal human organ sections, including pancreas, liver, lung, stomach, small intestine, spleen, lymph node, arteries, veins, skeletal muscle, heart, skin and fetal tissues were negative for tumor-associated antigens. Mucous substances and Panet's granular cells in colon mucosa showed nonspecific binding suppressible by addition of normal human serum. Adenocarcinoma of the stomach, colon, pancreas or breast did not demonstrate cross-reactivity with the antibodies to RCC. These monoclonal antibodies apparently recognize a tumor-associated antigen possibly specific for RCC. They could prove to be potent tools in the search for specific tumor markers applicable in the early diagnosis of the disease and immunotargeting cancer therapy.