BM 41.440: a new antineoplastic, antimetastatic, and immune-stimulating drug.

Abstract

Alkyllysophospholipids are analogs of the cell membrane component lysophosphocholine. The thioether lysophospholipid BM 41.440 (1-hexadecylmercapto-2-methoxymethyl-rac-glycero-3-phosphocholine) is already in use in phase I and II trials in human cancer therapy. A direct antitumor effect of this new compound has been shown in vitro using 35 different cell types of murine and human origin. All normal cells investigated were not affected in the concentration range (1-10 micrograms/ml) that was cytotoxic for most tumor cells studied. In vivo, antimalignant and antimetastatic actions have been documented in the Meth A sarcoma, L1210 leukemia, B 16 melanoma and the 3Lewis-lung carcinoma tumor models, respectively. Murine, bone marrow-derived macrophages (M phi), preincubated with BM 41.440, showed an increased cytotoxicity in vitro. Addition of syngeneic spleen cells and low doses of BM 41.440 to this system enhanced tumor cell destruction 20- to 100-fold compared to controls dependent on the target cells used (YAC, ABLS-8.1, L1210, and P815). In vivo, Meth A sarcoma growth was dose and time dependently reduced in CB6F1 mice under therapeutic IV application of BM 41.440-activated M phi. The mean survival time of DBA mice, treated once IP with BM 41.440 4 days before L1210 challenge, increased from 24 to 38 days.