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

C. L. Schwartz, Caterina 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

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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
StatePublished - 1987
Externally publishedYes

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Pentostatin
Monoclonal Antibodies
T-Lymphocytes
Bone Marrow Transplantation
Bone Marrow
Clinical Trials
Adenosine Deaminase
Autologous Transplantation
Hematopoietic Stem Cells
Cell Line

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Schwartz, C. L., Minniti, C. P., Harwood, P., Na, S., Banquerigo, M. L., Strauss, L. C., ... 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.

Elimination of clonogenic malignant human T cells using monoclonal antibodies in combination with 2'-deoxycoformycin. / Schwartz, C. L.; Minniti, Caterina P.; Harwood, P.; Na, S.; Banquerigo, M. L.; Strauss, L. C.; Kurtzberg, J.; Smith, S. D.; Civin, C. I.

In: Journal of Clinical Oncology, Vol. 5, No. 12, 1987, p. 1900-1911.

Research output: Contribution to journalArticle

Schwartz, CL, Minniti, CP, Harwood, P, Na, S, Banquerigo, ML, Strauss, LC, Kurtzberg, J, Smith, SD & Civin, CI 1987, 'Elimination of clonogenic malignant human T cells using monoclonal antibodies in combination with 2'-deoxycoformycin', Journal of Clinical Oncology, vol. 5, no. 12, pp. 1900-1911.
Schwartz, C. L. ; Minniti, Caterina P. ; Harwood, P. ; Na, S. ; Banquerigo, M. L. ; Strauss, L. C. ; Kurtzberg, J. ; Smith, S. D. ; Civin, C. I. / Elimination of clonogenic malignant human T cells using monoclonal antibodies in combination with 2'-deoxycoformycin. In: Journal of Clinical Oncology. 1987 ; Vol. 5, No. 12. pp. 1900-1911.
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AB - 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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