RESPONSE OF B-CELL LYMPHOMA TO A COMBINATION OF BISPECIFIC ANTIBODIESAND SAPORIN

Observations are described using a combination of two bispecific F(ab' )(2) antibodies (BsAb) to deliver the ribosome-inactivating protein, s aporin, in the treatment of few-grade, end-stage, B-cell lymphoma. Two BsAb were used, each having one arm directed at saporin and one at th e CD22 on target B cells. The BsAb, however, recognized different, non overlapping epitopes on each molecule, a strategy which permits high-a vidity double attachment of saporin to the target. The BsAb and sapori n were pre-mixed at a molar ratio of 3:1 24 h before treatment and inf used intravenously over a period of 1 h. Five patients have been treat ed, mostly with weekly doses of between 2 and 4 mg of saporin for a pe riod of up to 6 weeks. Toxicity was minimal. Three complained of weakn ess and myalgia for 1 to 2 days after treatment, without objective neu rological deficit or rise in serum creatine kinase. One patient produc ed an anti-mouse Fab' and an anti-saporin response. All patients showe d a rapid and beneficial response to treatment. When present, circulat ing tumor cells were cleared (4/4 patients), ascitic and pleural effus ions were eliminated (2/2 patients) and one patient with splenomegaly showed a marked reduction in tumor bulk. Malignant lymph nodes showed significant, but partial, shrinkage in all patients and finally marrow responded well with tumor clearance in biopsy material and impressive resolution of pancytopenia in some patients. While these responses we re mainly short-lived, with tumor progression once the treatment was s topped, their speed and magnitude, and the relative lack of associated toxicity warrants further study of this treatment to determine maximu m tolerated doses and therapeutic utility. Copyright (C) 1996 Publishe d by Elsevier Science Ltd.