Initial experience in treating human lymphoma with a chimeric univalent derivative of monoclonal anti-idiotype antibody

Murine monoclonal anti-idiotype antibody was raised against the surface IgM on the neoplastic cells of a patient with widespread follicular lymphoma. For therapy, a chimeric antibody derivative, FabIgG, was constructed by thioether-linking Fab'gamma, from the monoclonal antibody, to human normal IgG. FabIgG is univalent and thereby avoids rapid antigenic modulation. Its human IgG component is intended to optimize recruitment of effectors and metabolic survival while minimizing immunogenicity. Four intravenous (IV) infusions of 380 to 580 mg of anti-idiotype FabIgG were given over a period of 11 weeks. There was no significant toxicity. On each occasion, the antibody disappeared from the plasma with a half-life (t1/2) of less than 24 hours. The brief survival was evidently due to uptake by tumor, as infused control FabIgG, containing Fab'gamma from an irrelevant antibody, yielded a plasma t1/2 of greater than 10 days. With each therapeutic infusion, there was a fall in the number of circulating neoplastic cells over a 24-hour period. The numbers were largely replenished over the next week, but a net fall became discernible over the entire period of treatment. Four days after each infusion, nodal masses were swollen and tender, subsiding over approximately 8 days. At the end of the treatments, the blood lymphocyte count and nodal and splenic swellings continued to subside, so that by 6 weeks a partial remission with removal of greater than 50% of tumor was judged to have occurred. We did not detect any qualitative change in surface idiotype nor any antibody response to the infused Ig.

Initial experience in treating human lymphoma with a chimeric univalent derivative of monoclonal anti-idiotype antibody

Murine monoclonal anti-idiotype antibody was raised against the surface IgM on the neoplastic cells of a patient with widespread follicular lymphoma. For therapy, a chimeric antibody derivative, FabIgG, was constructed by thioether-linking Fab'gamma, from the monoclonal antibody, to human normal IgG. FabIgG is univalent and thereby avoids rapid antigenic modulation. Its human IgG component is intended to optimize recruitment of effectors and metabolic survival while minimizing immunogenicity. Four intravenous (IV) infusions of 380 to 580 mg of anti-idiotype FabIgG were given over a period of 11 weeks. There was no significant toxicity. On each occasion, the antibody disappeared from the plasma with a half-life (t1/2) of less than 24 hours. The brief survival was evidently due to uptake by tumor, as infused control FabIgG, containing Fab'gamma from an irrelevant antibody, yielded a plasma t1/2 of greater than 10 days. With each therapeutic infusion, there was a fall in the number of circulating neoplastic cells over a 24-hour period. The numbers were largely replenished over the next week, but a net fall became discernible over the entire period of treatment. Four days after each infusion, nodal masses were swollen and tender, subsiding over approximately 8 days. At the end of the treatments, the blood lymphocyte count and nodal and splenic swellings continued to subside, so that by 6 weeks a partial remission with removal of greater than 50% of tumor was judged to have occurred. We did not detect any qualitative change in surface idiotype nor any antibody response to the infused Ig.