Allogeneic T-cell compositions for induction of IL-12
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Publication Number
US-11045541-B2
Publication Date
2021-06-29
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 describes allogeneic activated T-cell compositions intended to induce endogenous IL-12 production in cancer patients while avoiding significant IL-12 toxicity. The approach uses mismatch Th1 cells that are activated and administered to skew the patient immune response toward a Th1 environment, thereby supporting the maturation of DC1 and IL-12 secretion by the patient’s antigen presenting cells (APC).
The mismatch Th1 cells are activated via CD3/CD28 cross-linking and include DC-maturation effector molecules such as CD40L. By promoting DC1 maturation, the patient’s APC produces endogenous IL-12 rather than relying on exogenous IL-12 delivery, which is framed in the provided content as enabling detectable IL-12 without significant IL-12 toxicity.
The described compositions and treatment concepts include multiple administration routes and dosing sequences, including intradermal priming, intratumoral dosing after tumor ablation as an in-situ vaccine concept, and intravenous dosing. IL-12 detection is monitored to evaluate timing and seroconversion, including non-clinical framing of IL-12 plasma measurements (e.g., ELISA and cytokine bead array) and an example study monitoring plasma IL-12 levels over time with reported pg/mL values.
Claims Coverage
The partial content provides one independent claim, covering an activated allogeneic Th1 cell composition with CD3/CD28 cross-linking using biodegradable bead-immobilized cross-linking agents, and dose numbers defined across intradermal, intratumoral, and intravenous routes. The inventive features in the independent claim focus on the composition structure, cross-linking arrangement, and multi-route dosing scheme.
Allogeneic activated Th1 cells with CD3/CD28 cross-linking
A composition comprising between one and six intradermal doses, between one and two intratumoral doses and between five and ten intravenous doses of activated allogeneic Th1 cells with cross-linking agents that cross-link CD3 and CD28 cell surface moieties.
Route-specific dose counts and cell concentration ranges
The intradermal doses comprise between 1×10^6 to 1×10^7 cells/ml, the intratumoral doses comprise between 1×10^7 to 1×10^8 cells/ml and the intravenous doses comprise between 1×10^7 to 1×10^9 cells/ml, respectively.
Biodegradable bead-immobilized CD3/CD28 cross-linking agents
The cross-linking agents are immobilized on surface of biodegradable beads and wherein the Th1 cells, the cross-linking agents and the biodegradable beads are suspended in a non-nutrient media.
Across the independent claim, the composition centers on activated allogeneic Th1 cells whose CD3 and CD28 are cross-linked by cross-linking agents immobilized on biodegradable beads, formulated as a non-nutrient media suspension, and administered via a defined set of intradermal, intratumoral, and intravenous doses with route-specific cell concentration ranges.
Stated Advantages
Induces endogenous IL-12 production in cancer patients without significant IL-12 toxicity.
Enables detectable IL-12 and improved survival when seroconversion occurs.
Documented Applications
Treatment of cancer patients using allogeneic activated Th1 cell compositions intended to induce endogenous IL-12 production.
A dose/ablation/injection sequence concept including intradermal priming and intratumoral dosing after tumor ablation as an in-situ vaccine concept, with IL-12 plasma monitoring over time.
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