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Department of Microbiology [E. S. V., R. M., M. T., V. G., J. W. U.] and Cancer Immunobiology Center [E. S. V.], University of Texas Southwestern Medical Center, Dallas, Texas 75235; Department of Oncology and Sammons Cancer Center [M. S., J. F., J. N., P. C., R. C.], Baylor University Medical Center, Dallas, Texas 75246; Drug Targeting Laboratory [P. E. T.], ICRF, London, United Kingdom; Departments of Oncology and Immunology [P. A.], Royal Free Hospital, London, United Kingdom; and Royal Marsden Hospital [D. C.], Sutton, Surrey, United Kingdom
Fifteen patients with refractory B-cell lymphoma were treated in a Phase I dose escalation clinical trial with a highly potent immunotoxin consisting of the Fab' fragment of a monoclonal anti-CD22 antibody (RFB4) coupled to chemically deglycosylated ricin A chain. All patients had low, intermediate, or high grade non-Hodgkin's lymphoma. The immunotoxin was administered i.v. in two to six doses at 48-h intervals. The peak serum concentration and the t
were not dose dependent among patients and averaged 1.3 µg/ml and 86 min, respectively. Three patients made antibody against A chain, and a fourth made antibody against both A chain and mouse immunoglobulin. Antibody responses were low (
85 µg/ml) in three patients and were not detected until 1 mo after treatment. The maximum tolerated dose of the immunotoxin was 75 mg/m2. Dose-related toxicities included vascular leak syndrome, fever, anorexia, and myalgia. Dose-limiting toxicities included pulmonary edema and/or effusion, expressive aphasia, and rhabdomyolysis (resulting in reversible kidney failure). There was no evidence of liver dysfunction. Partial responses were achieved in 38% of evaluable patients, and in those patients who had >50% CD22+ tumor cells, 50% of the patients achieved a partial response. Clinical responses were not related to tumor grade and were generally transient, lasting between 1 and 4 mo.
1 Supported by NIH Grants CA-28149 and CA-41081.
2 To whom requests for reprints should be addressed, at Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75235.
Received 2/15/91. Accepted 5/23/91.
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