Elimination of clonogenic malignant human T cells using monoclonal antibodies in combination with 2'-deoxycoformycin.
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.
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D003165:Complement System Proteins / Q000502:physiology; D003839:Deoxyadenosines / Q000494:pharmacology; D006801:Humans; D008212:Lymphocyte Depletion; D008223:Lymphoma / Q000473:pathology*; D015649:Pentostatin; D012263:Ribonucleosides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin; D003165:Complement System Proteins