Induction of IL-12 using immunotherapy
The present invention relates to compositions and methods that promote the induction of IL-12 in a patient. The composition includes activated allogeneic cells that are administered to a patient with a disease such as cancer. Administration of the composition skews the patient's immune response to a Th1 environment and produces detectable levels of IL-12 in the patient's plasma, without any IL-12 related toxicity.
1. A method of treating a patient with a solid tumor, the method comprising:
inducing the production of endogenous IL-12 in the patient, wherein the endogenous IL-12 is induced by administering a composition comprising activated allogeneic Th1 cells to the patient, wherein the Th1 cells are activated by cross-linking CD3 and CD28, wherein administration of the composition increases the level of IFN-gamma and the Th1 response in the patient;
measuring the plasma level of endogenous IL-12 in the patient; and
readministering the composition until endogenous IL-12 in the plasma of the patient is at least about 5000 pg/ml.
2. The method of claim 1 wherein the level of IL-12 is not toxic to the patient.
3. The method of claim 1 wherein the activated cells are CD4+ cells.
4. The method of claim 1 wherein the method further comprises readministering the composition until the level of endogenous IL-12 in the plasma of the patient is at least about 20,000 pg/ml.
5. The method of claim 1 wherein the composition is administered intravenously, intratumorally and/or intradermally.
6. The method of claim 1 wherein the method further comprises readministering the composition until the level of endogenous IL-12 in the plasma of the patient is at least about 8000 pg/ml.
7. The method of claim 1 wherein the method comprises ablating all or portion of a tumor in the patient to generate tumor necrosis prior to administration of the composition.
8. A method of treating a patient with a solid tumor, the method comprising:
inducing the production of endogenous IL-12 in the patient, wherein the endogenous IL-12 is induced by administering a composition comprising activated allogeneic Th1 cells to the patient, wherein the Th1 cells are activated by cross-linking CD3 and CD28;
ablating all or portion of a tumor in the patient to generate tumor necrosis along with intratumoral administration of the activated allogeneic Th1 cells;
measuring the level of endogenous IL-12 in the patient; and
readministering the composition until endogenous IL-12 in the plasma of the patient is at least about 5000 pg/ml.
9. The method of claim 8 wherein administration of the composition increases the level of IFN-gamma and Th1 response in the patient.
10. The method of claim 8 wherein the method further comprises readministering the composition until the level of endogenous IL-12 in the plasma of the patient is at least about 8000 pg/ml.