Elimination of clonogenic malignant human T cells using monoclonal antibodies in combination with 2'-deoxycoformycin

C. L. Schwartz, C. P. Minniti, P. Harwood, S. Na, M. L. Banquerigo, L. C. Strauss, J. Kurtzberg, S. D. Smith, C. I. Civin

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

2'Deoxycoformycin (dCF) specifically inhibits adenosine deaminase (ADA) and causes selective cytotoxicity of normal and malignant T cells. In clinical trials, dCF caused rapid lysis of malignant T lymphoblasts. Although dCF has been associated with dose-limiting nonhematopoietic toxicities, myelosuppression has not been observed. Since dCF is relatively nontoxic to hematopoietic stem cells, we tested dCF for utility in the ex vivo purging of malignant T lymphoblasts from remission leukemic bone marrow for autologous bone marrow transplantation. We found that T lymphoblast cell lines were sensitive to dCF (plus deoxyadenosine [dAdo]) under conditions that did not ablate human hematopoietic colony-forming cells. Moreover, combined pharmacologic (dCF plus dAdo) and immunologic (anti-T cell monoclonal antibodies [McAb] plus complement) purging resulted in additive reduction in clonogenic T lymphoblasts. These results provide the basis for a clinical trial of bone marrow transplantation using combined pharmacologic/immunologic purging of T lymphoblasts from patients' harvested autologous marrow.

Original languageEnglish (US)
Pages (from-to)1900-1911
Number of pages12
JournalJournal of Clinical Oncology
Volume5
Issue number12
DOIs
StatePublished - Jan 1 1987

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Schwartz, C. L., Minniti, C. P., Harwood, P., Na, S., Banquerigo, M. L., Strauss, L. C., Kurtzberg, J., Smith, S. D., & Civin, C. I. (1987). Elimination of clonogenic malignant human T cells using monoclonal antibodies in combination with 2'-deoxycoformycin. Journal of Clinical Oncology, 5(12), 1900-1911. https://doi.org/10.1200/JCO.1987.5.12.1900