Eradication of minimal disease in severe combined immunodeficient mice with disseminated Daudi lymphoma using chemotherapy and an immunotoxin cocktail

M. A. Ghetie, K. Tucker, J. Richardson, J. W. Uhr, E. S. Vitetta

Research output: Contribution to journalArticle

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Abstract

Severe combined immunodeficient (SCID) mice injected intravenously with a human Burkitt's lymphoma cell line (Daudi) develop disseminated lymphoma (SCID/Daudi), which is fatal in 100% of the mice. Early treatment of these mice with either an immunotoxin (IT) cocktail (consisting of anti-CD19-ricin A chain plus anti-CD22-ricin A chain) or chemotherapy significantly prolonged survival but was not curative. Combination therapy with the IT cocktail and any one of three chemotherapeutic drugs (doxorubicin, cytoxan, or camptothecin) cured the mice. Cure was demonstrated by both histopathologic examination of treated mice and, more importantly, by adoptive transfer of cells from organs of the cured mice to naive SCID mice where 100 tumor cells would have caused disease in the recipients. These results provide a strong rationale for combining IT therapy with conventional chemotherapy in the treatment of B-cell neoplasia.

Original languageEnglish (US)
Pages (from-to)702-707
Number of pages6
JournalBlood
Volume84
Issue number3
StatePublished - Aug 1 1994

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Disease Eradication
Immunotoxins
Chemotherapy
SCID Mice
Ricin
Lymphoma
Cells
Drug Therapy
Camptothecin
Doxorubicin
Cyclophosphamide
Tumors
Burkitt Lymphoma
Adoptive Transfer
Therapeutics
Neoplasms
B-Lymphocytes
Pharmaceutical Preparations
Cell Line
Survival

ASJC Scopus subject areas

  • Hematology

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Eradication of minimal disease in severe combined immunodeficient mice with disseminated Daudi lymphoma using chemotherapy and an immunotoxin cocktail. / Ghetie, M. A.; Tucker, K.; Richardson, J.; Uhr, J. W.; Vitetta, E. S.

In: Blood, Vol. 84, No. 3, 01.08.1994, p. 702-707.

Research output: Contribution to journalArticle

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AB - Severe combined immunodeficient (SCID) mice injected intravenously with a human Burkitt's lymphoma cell line (Daudi) develop disseminated lymphoma (SCID/Daudi), which is fatal in 100% of the mice. Early treatment of these mice with either an immunotoxin (IT) cocktail (consisting of anti-CD19-ricin A chain plus anti-CD22-ricin A chain) or chemotherapy significantly prolonged survival but was not curative. Combination therapy with the IT cocktail and any one of three chemotherapeutic drugs (doxorubicin, cytoxan, or camptothecin) cured the mice. Cure was demonstrated by both histopathologic examination of treated mice and, more importantly, by adoptive transfer of cells from organs of the cured mice to naive SCID mice where 100 tumor cells would have caused disease in the recipients. These results provide a strong rationale for combining IT therapy with conventional chemotherapy in the treatment of B-cell neoplasia.

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