Method for stimulating a host immune system
A method of manipulating allogeneic cells for use in allogeneic cell therapy protocols is described. The method provides a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism called the “Mirror Effect”. In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the “mirror” of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The “mirror” of the GVH effect is the host vs. graft (HVG) effect. The effectiveness and widespread application of the anti-tumor GVT effect is limited by the severe toxicity of the GVH effect. In the present invention, the anti-tumor HVT effect occurs in conjunction with a non-toxic HVG rejection effect. The highly activated allogeneic cells of the invention can be used in methods to stimulate host immunity. The method includes a complete HLA mis-matched setting in patients that have not had a prior bone marrow transplant or received chemotherapy and/or radiation conditioning regimens.
1. A method of treating a diseased host comprising:
stimulating the host's Type I adaptive immunity and generating de novo tumor associated antigen (TAA) shedding in the host wherein the stimulating is performed by the administration of activated allogeneic CD4+ cells.
2. The method of claim 1 wherein the CD4+ cells comprise cross-linked CD3 and CD28 surface molecules.
3. The method of claim 1 wherein the method further comprises activation and upregulation of cytotoxic activity of the host's NK cells.
4. The method of claim 1 wherein the TAA shedding is by apoptosis of the tumors.
5. The method of claim 4 wherein apoptosis is induced by binding of Fas with FasL.
6. The method of claim 4 wherein apoptosis is induced by TRAIL ligand and TRAIL-R.