Method for allogeneic cell therapy
A method of manipulating allogeneic cells for use in allogeneic cell therapy providing a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism, or “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 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 to stimulate host immunity in a complete HLA mis-matched setting in a patient.
1. A method for stimulating a host immune response against a tumor comprising:
selecting cells from a normal donor of which at least a portion are T-cells;
activating and formulating said donor cells ex vivo in media suitable for infusion into a host cancer patient, wherein said cells are activated by CD3 and CD28 surface antigen cross-linking; and
administering said activated donor cells to the host who has a 50% or less tissue match to said normal donor.
2. The method of claim 1 wherein the host immune response against the tumor includes the production of a “cytokine storm” including at least one of the following cytokines: IL-2, IL-15, TNF-alpha, TNF-beta, IL-12 and IFN-gamma.
3. The method of claim 2 wherein the selected normal donor cells are frozen prior to activation.
4. The method of claim 1 wherein the host immune response against the tumor includes activating innate cells including NK cells or macrophages.