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Publication Number
US-11883490-B2
Publication Date
2024-01-30
Expiration Date
Abstract
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.
Core Innovation
The invention provides a method of treating a patient with a solid tumor by inducing the production of endogenous IL-12 in the patient. Endogenous IL-12 is induced by administering a composition comprising activated allogeneic Th1 cells, where the Th1 cells are activated by cross-linking CD3 and CD28. The method includes measuring the level of endogenous IL-12 in the patient and readministering the composition based on the measured endogenous IL-12 level in the plasma.
The method further includes ablating all or a portion of the solid tumor in the patient to generate tissue necrosis. In conjunction with the ablation, intratumoral administration of the activated allogeneic Th1 cells is performed. The induced endogenous IL-12 is produced endogenously in the patient rather than being administered as exogenous IL-12.
The invention is also described as using activated allogeneic Th1 cells to skew the patient immune response to a Th1 environment and to induce detectable endogenous IL-12 in plasma without IL-12-related toxicity. The document ties IL-12 to IFN-gamma and Th1 anti-tumor immunity, with detectable and sustained endogenous IL-12 plasma levels over months as supported by longitudinal measurement results.
Claims Coverage
Independent claim 1 covers a treatment method that uses activated allogeneic Th1 cells activated by CD3/CD28 cross-linking to induce endogenous IL-12, in combination with tumor ablation and intratumoral administration, and uses endogenous IL-12 plasma measurement to drive readministration until a defined plasma threshold is reached. Dependent claims refine immunologic effects and adjust the readministration threshold.
Inducing endogenous IL-12 via activated allogeneic Th1 cells activated by CD3/CD28 cross-linking
Inducing the production of endogenous IL-12 in the patient by administering a composition comprising activated allogeneic Th1 cells, wherein the Th1 cells are activated by cross-linking CD3 and CD28.
Tumor ablation to generate tissue necrosis with intratumoral administration of activated allogeneic Th1 cells
Ablating all or portion of the solid tumor in the patient to generate tissue necrosis along with intratumoral administration of the activated allogeneic Th1 cells.
Measuring endogenous IL-12 and readministering until plasma endogenous IL-12 reaches a threshold
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.
Increasing IFN-gamma and Th1 response
The method is such that administering the composition increases IFN-gamma and the Th1 response in the patient.
Higher plasma threshold for readministration of endogenous IL-12
Readministering the composition until endogenous IL-12 in the patient’s plasma is at least about 8000 pg/ml.
Overall, the claim set centers on inducing endogenous IL-12 using activated allogeneic Th1 cells activated by CD3/CD28 cross-linking, performing tumor ablation to generate tissue necrosis with intratumoral administration, and using endogenous IL-12 plasma measurement to determine readministration until a specified IL-12 threshold is reached, with dependent refinement to increase IFN-gamma/Th1 response and to raise the readministration threshold.
Stated Advantages
Induces detectable endogenous IL-12 in plasma without IL-12-related toxicity.
Skews the patient immune response to a Th1 environment.
Induces an increased IFN-gamma and Th1 response in the patient.
Provides sustained endogenous IL-12 plasma levels over months.
Documented Applications
Treating a patient with a solid tumor using a method that induces endogenous IL-12 with activated allogeneic Th1 cells, includes tumor ablation to generate tissue necrosis with intratumoral administration, measures endogenous IL-12, and readministers the composition based on endogenous IL-12 plasma levels.
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