Methods and compositions for liquidation of tumors
This invention relates to compositions and methods for immunotherapy of cancer. Specifically, a method of cancer immunotherapy is described which results in the systemic liquidation of both solid and metastatic tumors whereever they reside in the body. The compositions include activated allogeneic Th1 cells that when administered appropriately lead to liquidation of tumors. The method includes administering priming doses of the therapeutic composition, ablation of a selected tumor lesion along with intratumoral injection of the composition and then infusion of the therapeutic composition. These steps enable the systemic liquidation of tumors secondary to immune cell infiltration and leads to immune-mediated tumor eradication.
1 . A therapeutic composition comprising at least three components, the three components comprising:
at least one foreign antigen;
at least one Type I inflammatory cytokine; and
at least one effector molecule capable of causing maturation of dendritic cells,
wherein at least one of the three components is not produced by or expressed by the same source of living cells.
2 . The composition of claim 1 wherein the foreign antigen is an alloantigen.
3 . The composition of claim 2 wherein the foreign antigen is from inactivated T-cells.
4 . The composition of claim 1 wherein the inflammatory cytokines are produced from living immune cells within the composition.
5 . The composition of claim 1 wherein the effector molecule is CD40L.
6 . The composition of claim 1 wherein the inflammatory cytokines are selected from one or more of the following: IFN-gamma, IL-2, TNF-alpha, TNF-beta, GM-CSF, IL-12.
7 . The composition of claim 1 wherein the effector molecule is expressed on the surface of immune cells.
8 . The composition of claim 1 suspended in a media suitable for infusion.
9 . The composition of claim 8 wherein the composition is packaged in a syringe.
10 . The composition of claim 1 , wherein the foreign antigen comprises xeno, allo, viral antigens or combinations thereof.
11 . The composition of claim 1 , wherein the at least one inflammatory cytokine is a recombinant protein, natural protein or combination thereof.
12 . The composition of claim 1 , wherein the effector molecule is a molecule that delivers a signal through CD40.
13 . The composition of claim 1 , wherein the therapeutic composition induces IL-12.
14 . The composition of claim 1 , wherein the therapeutic composition induces tumor liquidation.
15 . The composition of claim 1 , wherein the foreign antigen is soluble.
16 . The composition of claim 1 , wherein the foreign antigen is immobilized on a surface.
17 . A therapeutic composition consisting essentially of three types of components:
at least one foreign antigen;
at least one Type I inflammatory cytokine; and
at least one effector molecule capable of causing maturation of dendritic cells,
wherein at least one of the three components is not produced by or expressed by the same source of living cells.