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Elimination of clonogenic malignant human T cells using monoclonal antibodies in combination with 2'-deoxycoformycin. J Clin Oncol 1987 Dec;5(12):1900-11

Date

12/01/1987

Pubmed ID

3500279

DOI

10.1200/JCO.1987.5.12.1900

Scopus ID

2-s2.0-0023521490   5 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.

Author List

Schwartz CL, Minniti CP, Harwood P, Na S, Banquerigo ML, Strauss LC, Kurtzberg J, Smith SD, Civin CI

Author

Cindy L. Schwartz MD, MPH Chief, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Antibodies, Monoclonal
Antineoplastic Agents
Cell Line
Coformycin
Colony-Forming Units Assay
Complement System Proteins
Deoxyadenosines
Humans
Lymphocyte Depletion
Lymphoma
Pentostatin
Ribonucleosides
T-Lymphocytes
jenkins-FCD Prod-461 7d7c6113fc1a2757d2947d29fae5861c878125ab