Methods and compositions for inhibition of Treg cells
The present invention relates to methods of suppressing the immune tolerance of a disease or disease antigens in a patient. The method also promotes the activity of the effector T lymphocytes. The invention includes administering a therapeutic composition that promotes a Th1 environment in the patient while decreasing the immunosuppressive activity of Treg cells that can lead to disease antigen tolerance and immunoavoidance of the disease antigens by the patient. The therapeutic composition includes allogeneic emTh-1 cells. The therapeutic composition can also include disease antigens such as the chaperone-rich cell lysate of the disease antigen.
1 . A method of suppressing immune tolerance of a disease in a patient comprising:
decreasing the immunosuppressive activity of Treg cells by administering a therapeutic composition comprising allogeneic Th1 cells to a patient wherein decreasing and/or inhibiting the activity of the Treg cells reduces the immune tolerance of disease antigens in the patient.
2 . The method of claim 1 wherein the Treg cells are CD4+CD25+FoxP3+.
3 . The method of claim 1 wherein the suppressive activity of the Treg cells is inhibited by decreasing the conversion of naïve T cells (CD4CD25−FoxP3−) to iTreg cells.
4 . The method of claim 1 wherein the suppressive activity of the Treg cells is by inhibition of nTreg cells.
5 . The method of claim 1 wherein the therapeutic composition comprises allogeneic emTh1 cells.
6 . The method of claim 1 wherein the therapeutic composition further comprises disease antigens or lysates associated with the disease antigens.
7 . The method of claim 6 wherein the therapeutic composition further comprises chaperone rich cell lysate of the disease antigens.
8 . The method of claim 1 wherein the therapeutic composition further comprises IFNγ.
9 . The method of claim 1 wherein the therapeutic composition further comprises components that interact and reduce the activity of TGF-beta.
10 . The method of claim 1 wherein the therapeutic composition further comprises CD40L.
11 . The method of claim 1 wherein the disease is cancer.
12 . The method of claim 1 wherein the disease is an infectious disease.
13 . A method for stimulating a therapeutic immune effect in a patient comprising:
decreasing the immunosuppressive activity of Treg cells by administering a therapeutic composition comprising allogeneic Th1 cells to a patient wherein decreasing and/or inhibiting the activity of the Treg cells induces a therapeutic effect against the disease in the patient.
14 . The method of claim 13 wherein the Treg cells are CD4+CD25+FoxP3+.
15 . The method of claim 13 wherein the suppressive activity of the Treg cells is inhibited by decreasing the conversion of naïve T cells (CD4CD25−FoxP3−) to iTreg cells.
16 . The method of claim 13 wherein the suppressive activity of the Treg cells is by inhibition of nTreg cells.
17 . The method of claim 13 wherein the therapeutic composition comprises allogeneic emTh-1 cells.
18 . The method of claim 13 wherein the therapeutic composition further comprises disease antigens or lysates associated with the disease antigens.
19 . The method of claim 18 wherein the therapeutic composition further comprises chaperone rich cell lysate of the disease antigens.
20 . The method of claim 13 wherein the therapeutic composition further comprises IFNγ.
21 . The method of claim 13 wherein the therapeutic composition further comprises components that interact and reduce the activity of TGF-beta.
22 . The method of claim 13 wherein the therapeutic composition further comprises CD40L.
23 . The method of claim 13 wherein the disease is cancer.
24 . The method of claim 13 wherein the disease is an infectious disease.
25 . The method of claim 13 wherein the therapeutic effect comprises promoting anti-tumor function of effector T cells and suppressing immune tolerance of the disease antigens.
26 . A method of impairing the immunosuppressive functions in a patient comprising:
decreasing the immunosuppressive activity of Treg cells by administering a therapeutic composition comprising allogeneic Th1 cells to a patient wherein decreasing and/or inhibiting the activity of the Treg cells reduces the immunosuppressive functions in the patient.
27 . The method of claim 26 wherein the Treg cells are CD4+CD25+FoxP3+.
28 . The method of claim 26 wherein the suppressive activity of the Treg cells is inhibited by decreasing the conversion of naïve T cells (CD4CD25−FoxP3−) to iTreg cells.
29 . The method of claim 26 wherein the suppressive activity of the Treg cells is by inhibition of nTreg cells.
30 . The method of claim 26 wherein the therapeutic composition comprises allogeneic emTh-1 cells.
31 . The method of claim 26 wherein the therapeutic composition further comprises disease antigens or lysates associated with the disease antigens.
32 . The method of claim 31 wherein the therapeutic composition further comprises chaperone rich cell lysate of the disease antigens.
33 . The method of claim 26 wherein the therapeutic composition further comprises IFNγ.
34 . The method of claim 26 wherein the therapeutic composition further comprises components that interact and reduce the activity of TGF-beta.
35 . The method of claim 26 wherein the therapeutic composition further comprises CD40L.
36 . The method of claim 26 wherein the disease is cancer.
37 . A method of suppressing immune tolerance and promoting a therapeutic effect in patients with a disease comprising administering activated Th1 cells and a source of disease antigens wherein the Th1 cells and the disease antigens are administered at the same location.
38 . The method of claim 37 wherein the Th1 cells and the disease antigens are administered by intradermal injections.
39 . The method of claim 37 wherein the activated Th1 cells are administered prior to the source of disease antigens.
40 . The method of claim 37 wherein the Th1 cells are allogeneic emTh-1 cells.
41 . The method of claim 37 wherein the source of disease antigens is CRCL.
42 . The method of claim 37 wherein the Th1 cells and the source of disease antigens are administered at least 3 times and at intervals of about 3-10 days until the patient exhibits a therapeutic effect.
43 . A composition comprising a source of disease antigens and an adjuvant wherein the disease antigens are contained within chaperone proteins and the adjuvant comprises activated allogeneic Th1 cells.