Preclinical studies on deoxycoformycin and deoxyadenosine as pharmacologic T cell purging tools.
Deoxycoformycin (dCf) is a potent toxin to T lymphocytes in human peripheral blood and bone marrow. In the presence of deoxyadenosine (dAdo), dCf inhibits T cell function as measured by DNA synthesis induced by stimuli in the rank order of mixed lymphocyte culture greater than murine monoclonal antibody OKT3 greater than phytohemagglutinin. Approximately two logs of human bone marrow T cells were removed by 24 h of incubation with dCf and dAdo at doses that preserved colony-forming ability of the treated marrow. A semi-closed system of isolating mononuclear cells in large volumes using density gradient centrifugation was developed. Using this system, it was found that dCf and dAdo could remove about two logs of T lymphocytes after 24 h of incubation when the cells were incubated in large volumes at a relatively high concentration (10(7) cells/ml). This system appears well suited for purging T lymphocytes from human bone marrow before clinical transplantation.
Sheridan
W
W
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322.
Gordon
D S
DS
Fullen
A J
AJ
Olson
A
A
Vogler
W R
WR
Winton
E
E
D058892:Adenosine Deaminase Inhibitors; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D003114:Colony-Forming Units Assay; D003470:Culture Media; D003839:Deoxyadenosines / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008212:Lymphocyte Depletion; D015649:Pentostatin / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*
D058892:Adenosine Deaminase Inhibitors; D003470:Culture Media; D003839:Deoxyadenosines; D015649:Pentostatin