Toxin-Based Therapeutic Approaches

Shapira, Assaf; Benhar, Itai

CD22 is a 135-kDa phosphoglycoprotein adhesion molecule present on the surface of B cells, including human B-cell lymphomas and leukemias [185] [186] [187] [188] [189] . RFB4(dsFv)-PE38 (BL22) is a stable immunotoxin targeted against CD22 expressing cells, and is composed of disulfide stabilized Fv regions (dsFv) of the anti-CD22 monoclonal antibody RFB4 [190] fused to PE38 [191] . Clinical trials with i.v. administrated BL22 in adults with hairy cell leukemia resistant to purine analogue therapy, produced promising results with 19 complete remissions (61%) and six partial responses (19%) in 31 patients in Phase I [45] , and 25% complete remission, 25% partial response after one cycle of treatment in Phase II (n = 36) [46] . The most common toxicities included hypoalbuminemia, transaminase elevations, fatigue, edema and reversible grade 3 hemolytic uremic syndrome, not requiring plasmapheresis. A recent Phase I clinical trial that was conducted for pediatric subjects with CD22 + ALL and non-Hodgkin lymphoma [47] showed that the treatment was associated with an acceptable safety profile and adverse events were rapidly reversible. No maximum tolerated dose was defined, and although no responses were observed, transient clinical activity was seen in most subjects [192] [193] [194] .