Pharmacological elimination of tumor cells contaminating normal human bone marrow using PTT-119.
In this study, we evaluated the inhibitory effects of PTT-119, a new tripeptide which is known to be a bifunctional alkylating agent, on two tumor cell lines with different origins: SK-DHL-2 (B-cell diffuse histiocytic lymphoma cell line) and RPMI 8226 (Multiple myeloma patient cell line) and compared the toxicity of PTT-119 toward normal human bone marrow granulocyte macrophage (CFU-GM), erythroid (BFU-E), and pluripotent (CFU-GEM) progenitors. Reduction of at least four logs was achieved on clonogenic myeloma cells after 1 hr of treatment with 25 micrograms/mL of PTT-119 either in the presence or absence of irradiated bone marrow (BM) cells. More than three and at least four logs of lymphoma cell kill were found after 1 hr of incubation with 25 and 40 micrograms/mL of the tripeptide, respectively. PTT-119 antitumor effects on SK-DHL-2 were only slightly affected in the presence of an excess of BM cells. BM cells treated for 1 hr with 25 micrograms/mL of PTT-119 showed a mean recovery of 4.5, 3.8, and 13.8% of CFU-GM, BFU-E, and CFU-GEM, respectively. The addition of 5- and 10-fold excesses of red blood cells (RBC) produced a slightly higher recovery of these hematopoietic progenitors. These results suggest that PTT-119 may be useful as a chemotherapeutic agent for the ex vivo treatment of bone marrow grafts.
Lemoli
R M
RM
Laboratories of Hematopoietic Cell Kinetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Gulati
S C
SC
Perez
A
A
Clarkson
B D
BD
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D001402:B-Lymphocytes / Q000473:pathology; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000473:pathology*; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology*; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology* / Q000633:toxicity; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; C038259:ambamustine