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 journalArticlepeer-review

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 - 1987

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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