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Successful treatment of disseminated human Hodgkin's disease in SCID mice
with deglycosylated ricin A-chain immunotoxins
U Winkler, C Gottstein, G Schon, U Kapp, J Wolf, ML Hansmann, H Bohlen, P Thorpe, V Diehl and A Engert
Medizinische Universitatsklinik I, Koln, Germany.
To evaluate the effects of deglycosylated ricin A-chain (dgA) immunotoxins
against disseminated Hodgkin's lymphoma, we used RFT5.dgA (CD25) and
IRac.dgA (70 kD) to treat L540Cy Hodgkin cells in severely immunodeficient
SCID mice. In this model, more than 90% of the animals developed multiple
lymphomas in various organs such as the lymph nodes, liver, bone marrow,
and extranodal sites that killed untreated animals after a mean survival
time (MST) of 36.3 days. A single intraperitoneal injection of 8 micrograms
of either immunotoxin rendered 95% (RFT5.dgA) and 93% (IRac.dgA),
respectively, of mice tumor-free when applied 1 day after tumor challenge.
The MST of the RFT5.dgA-treated group was extended by more than 80 days (P
< .00001). SCID mice treated 12 days after tumor challenge had lower
remission rates (46%), suggesting that the antitumor effect of the
immunotoxins depends on the number of tumor cells present. We conclude that
ricin A-chain immunotoxins have potent antitumor effects against
disseminated Hodgkin's tumors in SCID mice and that this model is ideally
suited for the evaluation of different immunotoxin treatment modalities.
Volume 83,
Issue 2,
pp. 466-475,
01/15/1994
Copyright © 1994 by The American Society of Hematology
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