Method for stimulating a therapeutic immune effect in a patient
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 to stimulate host immunity in 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 for stimulating a therapeutic immune effect in a patient comprising:
collecting cells from a donor other than the patient with at least a portion of the cells being T-cells;
cross-linking CD3 and CD28 surface antigens on the T-cells to activate the T-cells; and
infusing the activated T-cells with the cross-linked CD3 and CD28 surface antigens into the patient.
2. The method of claim 1 where the therapeutic immune effect is an anti-tumor or anti-viral or anti-parasitic immune effect.
3. The method of claim 1 , where the CD3/CD28 cross-linking occurs within 8 hours of infusion.
4. The method of claim 1 , where the CD3/CD28 cross-linking occurs within 6 hours of infusion.
5. The method of claim 1 , where the CD3/CD28 cross-linking occurs within 4 hours of infusion.
6. The method of claim 1 , where the CD3/CD28 cross-linking occurs with the T-cells in infusion media.
7. The method of claim 6 , where the cells are at a density >10 7 /ml.
8. The method of claim 1 where the infusion of said activated cells is intravenous.
9. The method of claim 1 where the infusion of said activated cells is intradermal.
10. The method of claim 1 where the infusion of said activated cells is intraosseal.
11. The method of claim 1 where the infusion of said activated cells is intranodal.
12. The method of claim 1 where the CD3/CD28 antigens are cross-linked by contact with antibodies reactive to said antigens and immobilized on a biodegradable support.
13. The method of claim 1 where the patient is intentionally mismatched to the donor.
14. A method for stimulating a therapeutic immune effect in a patient comprising: infusing activated T-cells with cross-linked CD3 and CD28 surface antigens into the patient, wherein the T-cells are a portion of the cells collected from a donor other than the patient and the T-cells are activated by cross-linking the CD3 and CD28 surface antigens on the T-cells.
15. The method of claim 14 where the therapeutic immune effect is an anti-tumor or anti-viral or anti-parasitic immune effect.
16. The method of claim 14 , where the CD3/CD28 cross-linking occurs within 8 hours of infusion.
17. The method of claim 14 , where the CD3/CD28 cross-linking occurs with the T-cells in infusion media.
18. The method of claim 14 where the CD3/CD28 antigens are cross-linked by contact with antibodies reactive to said antigens and immobilized on a biodegradable support.
19. The method of claim 14 where the patient is intentionally mismatched to the donor.