IMMUNOTOXIN PROTOCOLS--TARGETED THERAPY OF LYMPHOID NEOPLASMS

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"This project area builds on previous observations (Blood 85: 3457, 1995 and Blood 88:1188, 1996) that immunotoxins constructed with deglycosylated ricin A chain and murine monoclonal antibodies directed to anti-CD22 and anti-CD19 determinants respectively could be given safely to patients and in the case of the anti-CD22 reagent cause meaningful responses. During the period covered by this report, we completed a Phase I study of the combination of the anti-CD19 + anti-CD22 immunotoxins, based on pre clinical data that the combination might be more effective. Unfortunately, we encountered dose-limiting toxicity in a way that did not correlate with dose. This consisted of vascular leak syndrome and a hemolytic-uremic syndrome in previously irradiated patients. Laboratory studies support the concept that aggreggation of the CD19 immunotoxin also may have contributed to this phenomenon. Preclinical studies have defined a safe storage and thawing procedure that minimizes aggregation of immunotoxin. A current Phase I is now focusing on highly purified versions of the anti- CD22 construct which has two deglycosylated ricin A chains per immunoglobulin molecule. This is being studied as a single agent in the case of the double A chain molecule, and in combination with chemotherapy in the case of the mono-ricin A chain adduct."