POTENT ANTITUMOR EFFECTS OF AN ANTI-CD24 RICIN A-CHAIN IMMUNOTOXIN IN-VITRO AND IN A DISSEMINATED HUMAN BURKITTS-LYMPHOMA MODEL IN SCID MICE

A new anti-CD24 immunotoxin (IT), SWAII.dgA, was constructed by coupli ng the MAb SWAII via the bivalent linker SMPT to deglycosylated ricin A-chain (dgA). The effects of SWAII.dgA were evaluated in vitro agains t the B-precursor leukemia cell line REH, the non-B-non-T acute lympho blastic leukemia cell line NALM-6 and the Burkitt's lymphoma cell line s BL-2 and BL-38. Binding of SWAII to the CD24 antigen was assessed by flow cytometry demonstrating high affinity of the MAb for all cell li nes tested. SWAII.dgA inhibited the protein synthesis of BL-38, NALM-6 , REH and BL-2 cells by 50% at concentrations (IC50) of 4.0 x 10(-11) M, 6.0 x 10(-11) M, 8.0 x 10(-11) M and 3.0 x 10(-9) M, respectively. SWAII.dgA was subsequently used for the treatment of disseminated huma n BL-38 Burkitt's lymphoma in a newly developed SCID mouse model. The mean survival time (MST) of BL-38-bearing SCID mice was extended from 23 days in untreated controls to more than 230 days when 6 mu g SWAII. dgA was applied intraperitoneally one day after tumor challenge. All o f the animals achieved continuous complete remissions. SCID mice treat ed with SWAII.dgA 4 days after tumor cell challenge or a reduced dose of SWAII.dgA (67%) also had a significantly extended MST (45.0 and 51. 4 days, respectively, as compared to 22.7 and 23.1 days in the control s). We conclude that SWAII.dgA might be of potential use for the treat ment of lymphoma in man. (C) 1996 Wiley-Liss, Inc.