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Journal of Clinical Oncology, Vol 5, 1900-1911, Copyright © 1987 by American Society of Clinical Oncology

ARTICLES

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

CL Schwartz, CP Minniti, P Harwood, S Na, ML Banquerigo, LC Strauss, J Kurtzberg, SD Smith and CI Civin
Division of Pediatric Oncology, Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, Baltimore.

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.
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Copyright © 1987 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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