Combination preparation of a biological response modifier and an anticancer agent and uses thereof

Abstract

The present invention provides anticancer biological response modifier combinations. In accordance with an aspect of the present invention, there is provided a combination comprising: (i) a composition comprising small molecular weight components of less than 3000 daltons, and having the following properties: is extracted from bile of animals; is capable of stimulating monocytes and/or macrophages in vitro and/or in vivo; is capable of modulating tumor necrosis factor production and/or release; contains no measurable level of IL-1α, IL-1β, TNF, IL-6, IL-8, IL-4, GM-CSF or IFN-gamma; is not cytotoxic to human peripheral blood mononuclear cells; is not an endotoxin; and (ii) one or more anticancer agent(s), wherein said combination has therapeutic synergy or improves the therapeutic index in the treatment of cancer over the composition or the anticancer agent(s) alone. Another aspect of the present invention provides the use of this combination in the manufacture of a medicament or a pharmaceutical kit and in the treatment of cancer.

Description

FIELD OF THE INVENTION [0001] The present invention relates to anticancer biological response modifier combinations, pharmaceutical compositions comprising the same, and the use thereof in the treatment of cancer. BACKGROUND OF THE INVENTION [0002] There are a number of therapies directed towards the treatment of cancer, including chemotherapeutic drugs, radiation, gene therapy and antisense oligonucleotides. One drawback to current therapies is the toxicity associated with most treatments. Moreover, oftentimes large dosages must be administered over an extended period of time in order to attain therapeutic benefit. Thus, a need remains for more effective treatments. [0003] A bile extract has been prepared that is known to be able to modify the biological response of cells of the immune system. The production and characterization of this bile-derived Biological Response Modifier (BD-BRM) has been described in International Patent Application Ser. No. PCT / CA94 / 00494, published Feb. 1...

AI Technical Summary

Benefits of technology

[0026] An object of the present invention is to provide anticancer biological response modifier combinations. In accordance with an aspect of the present invention, there is provided a combination comprising: (i) a composition comprising small molecular weight components of less than 3000 daltons, and having the following properties: is extracted from bile of animals; is capable of stimulating monocytes and/or macrophages in vitro and/or in vivo; is capable of modulating tumor necrosis factor production and/or release; contains no measurable level of IL-1α, IL-1β, TNF, IL-6, IL-8, IL-4, GM-CSF or IFN-gamma; is not cytotoxic to human peripheral blood mononuclear cells; is not an endotoxin; and (ii) one or more anticancer agent(s), wherein said combination has therapeutic synergy or improves the therapeutic index in the treatment of cancer over the composition or the anticancer agent(s) alone. Another aspect of the present invention provides the use of this combination in the manufacture of a medicament or a pharmaceutical kit.

[0027] In accordance with another aspect of the invention, there is provided a pharmaceutical kit comprising: (i) a dosage unit of a composition and a pharmaceutically acceptable carrier wherein the composition comprises small molecular weight components of less than 3000 daltons, and has the following properties: is extracted from bile of animals; is capable of stimulating monocytes and/or macrophages in vitro and/or in vivo; is capable of modulating tumor necrosis factor production and/or release; contains no measurable level of IL-1α, IL-1β, TNF, IL-6, IL-8, IL-4, GM-CSF or IFN-gamma; is not cytotoxic to human peripheral blood mononuclear cells; is not an endotoxin; and (ii) a dosage unit of one or more chemotherapeutic drug(s) and a pharmaceutically acceptable carrier, (i) and (ii) being provided in amounts that are effective, in combination, for killing tumour or metastatic cells.

[0028] In accordance with another aspect of the invention, there is provided a pharmaceutical composition comprising: (i) a composition comprising small molecular weight components of less than 3000 daltons, and having the following properties: is extracted from bile of animals; is capable of stimulating monocytes and/or macrophages in v

Problems solved by technology

One drawback to current therapies is the toxicity associated with most treatments.

This is considered importan

Images