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. We had previously 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. These studies have recently been published(Clin. Cancer Res. 6:1302-1313, 2000). The future plan is to focus on a highly purified """"""""monovalent"""""""" immunotoxin where one A chain is joined to one antibody molecule as a single agent. The protocol to accomplish this has been approved by the NCI IRB and will commence in late 2000.

Agency
National Institute of Health (NIH)
Institute
Division of Clinical Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01SC006744-06
Application #
6433124
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Clinical Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code