Abstract

The aim of this program project is to initiate clinical trials using ricin A chain-containing immunotoxins (A-IT). Anti-delta-A-IT will be administered intravenously to patients sIgD B cell lymphomas and leukemias. In subsequent clinical trials, lysosomotropic agents and B-chain IT will be used to potentiate A-IT targent cell toxicity. These studies will necessitate the preparation and characterization of large amounts of highly purified A and B chain, anti-delta antibody, anti-antibody and the resulting ITs. Using sensitive clonal assays, the ITs will be tested for potency in killing sIgD tumor cells in vitro, as well as, their nonspecific toxicity in rodents and primates. The primary goal of the initial trial will be to determine and solve the problems resulting from the use of these ITs. If the A-IT does not induce side effects, then subsequent phase II trials will be performed.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA041081-04
Application #
3093825
Study Section
(SRC)
Project Start
1986-01-01
Project End
1990-12-31
Budget Start
1989-05-01
Budget End
1989-12-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Texas Sw Medical Center Dallas
Department
Type
Overall Medical
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390

  Publications

Schindler, J; Sausville, E; Messmann, R et al. (2001) The toxicity of deglycosylated ricin A chain-containing immunotoxins in patients with non-Hodgkin's lymphoma is exacerbated by prior radiotherapy: a retrospective analysis of patients in five clinical trials. Clin Cancer Res 7:255-8
Schnell, R; Vitetta, E; Schindler, J et al. (2000) Treatment of refractory Hodgkin's lymphoma patients with an anti-CD25 ricin A-chain immunotoxin. Leukemia 14:129-35
Schnell, R; Vitetta, E; Schindler, J et al. (1998) Clinical trials with an anti-CD25 ricin A-chain experimental and immunotoxin (RFT5-SMPT-dgA) in Hodgkin's lymphoma. Leuk Lymphoma 30:525-37
Senderowicz, A M; Vitetta, E; Headlee, D et al. (1997) Complete sustained response of a refractory, post-transplantation, large B-cell lymphoma to an anti-CD22 immunotoxin. Ann Intern Med 126:882-5
Baluna, R; Sausville, E A; Stone, M J et al. (1996) Decreases in levels of serum fibronectin predict the severity of vascular leak syndrome in patients treated with ricin A chain-containing immunotoxins. Clin Cancer Res 2:1705-12
Stone, M J; Sausville, E A; Fay, J W et al. (1996) A phase I study of bolus versus continuous infusion of the anti-CD19 immunotoxin, IgG-HD37-dgA, in patients with B-cell lymphoma. Blood 88:1188-97
Ghetie, M A; Podar, E M; Gordon, B E et al. (1996) Combination immunotoxin treatment and chemotherapy in SCID mice with advanced, disseminated Daudi lymphoma. Int J Cancer 68:93-6
Shen, G L; Li, J L; Vitetta, E S (1994) Bispecific anti-CD22/anti-CD3-ricin A chain immunotoxin is cytotoxic to Daudi lymphoma cells but not T cells in vitro and shows both A-chain-mediated and LAK-T-mediated killing. J Immunol 152:2368-76
Ghetie, M A; Picker, L J; Richardson, J A et al. (1994) Anti-CD19 inhibits the growth of human B-cell tumor lines in vitro and of Daudi cells in SCID mice by inducing cell cycle arrest. Blood 83:1329-36
Soler-Rodriguez, A M; Ghetie, M A; Oppenheimer-Marks, N et al. (1993) Ricin A-chain and ricin A-chain immunotoxins rapidly damage human endothelial cells: implications for vascular leak syndrome. Exp Cell Res 206:227-34

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