Production of Cytokine-Specific Monoclonal Antibodies that Modulate Immune and Inflammatory Processes.

The goal of this cooperative agreement has been to generate, characterize and produce large quantities of purified monoclonal antibodies mAb that are endotoxin and aggregate-free. We have now perfected our large scale tissue culture techniques and scale-up HPLC Protein A affinity chromatography techniques suitable for the production of greater than or equal 2OO mg quantities of mAb. Over 600 mg of purified mAb has already been supplied to the Army for research purposes, thus fulfilling the first specific aim of the project. We have also now generated and completely characterized a novel family of hamster mAb specific for either the p55 or p75 murine TNF receptors. Among these reagents are mAb which can either inhibit TNF activity antagonist, or can alone, mimic TNF activity agonist. This panel of reagents has provided the opportunity to trigger receptor-specific activities while avoiding unwanted or toxic reactions elicited with cytokine alone. We continue to investigate whether these reagents represent a therapeutic modality to permit desirable actions of a cytokine while at the same time preventing pathobiologic actions. Thus, we believe that we have achieved the initial goals of the project and continue to investigate the potential of these novel mAb.