Successful treatment of disseminated human Hodgkin's disease in SCID mice with deglycosylated ricin A-chain immunotoxins

U. Winkler, C. Gottstein, G. Schön, U. Kapp, J. Wolf, M. L. Hansmann, H. Bohlen, P. Thorpe, V. Diehl, A. Engert

Research output: Contribution to journalArticle

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Abstract

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 μg 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.

Original languageEnglish (US)
Pages (from-to)466-475
Number of pages10
JournalBlood
Volume83
Issue number2
StatePublished - Jan 15 1994

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Ricin
Immunotoxins
SCID Mice
Hodgkin Disease
Tumors
Neoplasms
Therapeutics
Animals
Intraperitoneal Injections
Liver
Lymphoma
Bone
Cell Count
Lymph Nodes
Bone Marrow
Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Winkler, U., Gottstein, C., Schön, G., Kapp, U., Wolf, J., Hansmann, M. L., ... Engert, A. (1994). Successful treatment of disseminated human Hodgkin's disease in SCID mice with deglycosylated ricin A-chain immunotoxins. Blood, 83(2), 466-475.

Successful treatment of disseminated human Hodgkin's disease in SCID mice with deglycosylated ricin A-chain immunotoxins. / Winkler, U.; Gottstein, C.; Schön, G.; Kapp, U.; Wolf, J.; Hansmann, M. L.; Bohlen, H.; Thorpe, P.; Diehl, V.; Engert, A.

In: Blood, Vol. 83, No. 2, 15.01.1994, p. 466-475.

Research output: Contribution to journalArticle

Winkler, U, Gottstein, C, Schön, G, Kapp, U, Wolf, J, Hansmann, ML, Bohlen, H, Thorpe, P, Diehl, V & Engert, A 1994, 'Successful treatment of disseminated human Hodgkin's disease in SCID mice with deglycosylated ricin A-chain immunotoxins', Blood, vol. 83, no. 2, pp. 466-475.
Winkler U, Gottstein C, Schön G, Kapp U, Wolf J, Hansmann ML et al. Successful treatment of disseminated human Hodgkin's disease in SCID mice with deglycosylated ricin A-chain immunotoxins. Blood. 1994 Jan 15;83(2):466-475.
Winkler, U. ; Gottstein, C. ; Schön, G. ; Kapp, U. ; Wolf, J. ; Hansmann, M. L. ; Bohlen, H. ; Thorpe, P. ; Diehl, V. ; Engert, A. / Successful treatment of disseminated human Hodgkin's disease in SCID mice with deglycosylated ricin A-chain immunotoxins. In: Blood. 1994 ; Vol. 83, No. 2. pp. 466-475.
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