A novel anticancer agent, benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride, activates multiple immunologic mechanisms of an antitumor response.

Abstract

e12024 Background: BP-C1 (a combination of a benzene polycarboxylic acids complex (BP-Cx-1) with cis-diamineplatinum in a very low concentration) was demonstrated to be safe and effective in the treatment of stage IV breast cancer. Methods: In order to investigate whether the immune system mediates some of the clinical activity of BP-C1, we conducted an in vitro study of the immune modulating properties of this compound. The study was done using peripheral blood mononuclear cells from healthy donors. Results: It was demonstrated that the production of a number of cytokines was significantly increased by BP-C1, first of all IL-1beta, TNF-alpha, GM-CSF, IFN-gamma, and IL-25. The carrier molecule, BP-Cx-1, alone also stimulated IL-6 production. Experiments with isolated cultures of monocytes and lymphocytes indicated that the primary targets for these reagents are monocytes. Activation of monocytes leads to two major effects: a) the production of cytokines that are able to increase the anti-tumor activity of lymphocytes, and b) the acquired ability of monocytes to inhibit tumor cell growth. In addition, direct effects on lymphocytes were also demonstrated, exemplified by the induction of IL-25 production. Conclusions: In conclusion, it was demonstrated that BP-C1 and the related compounds are able to activate multiple immunological mechanisms of anti-tumor response.