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. 1991 Sep;117(5):403–408. doi: 10.1007/BF01612758

Investigation into the immunological effects of miltefosine, a new anticancer agent under development

P Hilgard 1,✉, E Kampherm 1, L Nolan 1, J Pohl 1, T Reissmann 1
PMCID: PMC12201705  PMID: 1890137

Abstract

Miltefosine is the prototype of alkylphospho-cholines, a new class of anticancer agents related to alkyllysophospholipids. These agents were considered to possess potent immunomodulatory properties. Miltefosine was highly active against the human KB tumour xenograft in nude mice, leading to growth inhibition as well as regression of large established tumours, which suggested that its mode of action was not mediated by the T cell system. In vivo natural killer cell activity was measured by chromium release of YAC-1 cells using spleen cells from treated animals as effector cells. Miltefosine had no significant effect on YAC-1 cytolysis. Similarly, the compound did not induce cytotoxic spleen cells against KB target cells. The results were identical when spleen cells from tumour-bearing animals were used. Humoral antibody production in rats following sheep red blood cell immunization was not changed by miltefosine pretreatment. Finally, the in vitro phagocytic activity of mouse bone marrow macrophages was not stimulated but rather inhibited in a dose-dependent manner. In conclusion, there is no experimental evidence that the miltefosine action is mediated by the host immune system and no major immunotoxicity was observed.

Key words: Miltefosine, NK cells, Humoral antibodies, Phagocytosis

Abbreviations

DMEM

Dulbecco's modified Eagle's medium

FCS

fetal calf serum

poly(I)·poly(C)

polyinosinic·polycytidilic acid

SRBC

sheep red blood cells

ET-18-OCH3

octadecylmethoxy-sn-rac-glycerophosphocholine

NK

natural killer

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