Composition for treating inflammatory disease induced by hyperimmune response
Inventors
CHOI, Heonsik • CHOI, Kyoungbaek • LEE, Hyeonyoul • Kim, Daewook • Lee, Hyesun • Kim, Min • Kim, Sujeong
Assignees
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Publication Number
US-11191787-B2
Publication Date
2021-12-07
Expiration Date
Abstract
Provided is a cell therapeutic agent for treating an inflammatory disease induced by a hyperimmune response, more specifically, a composition for treating an inflammatory disease induced by a hyperimmune response, which comprises (i) a chondrocyte or a cell capable of differentiating into a chondrocyte; and (ii) a cell into which a gene encoding TGF-β is introduced, wherein the cell in (ii) is derived from human embryonic kidney 293 (HEK-293) cell.
Core Innovation
The disclosed invention relates to a cell therapeutic composition and methods for treating inflammatory diseases driven by hyperimmune responses, including rheumatoid arthritis. The composition includes a chondrocyte or a chondrocyte-differentiating cell and a human cell engineered to express TGF-β, identified as hChonJb#7.
The disclosed rationale is directed to modulating an inflammatory microenvironment by acting on macrophage phenotypes and cytokine profiles. The described mechanism includes induction of M2 macrophages and the formation of an anti-inflammatory IL-10-rich environment, including increased arginase 1.
Preclinical animal data described in the partial content report reduced pain and edema and decreased synovial cytokines after mixed-cell administration. The document further reports duration of effects and histological cartilage regeneration findings, including observations consistent with cartilage regeneration and type II collagen and hyaline cartilage outcomes.
Claims Coverage
The partial content includes two independent claims, both directed to treating rheumatoid arthritis by administering a composition directly to an articular cavity. Across the independent claims, the inventive core is the combination of a chondrocyte with hChonJb#7 and the claimed inhibition of IL-6, IL-17A, IL-1β, and TNF-α in synovial lavage fluid.
Direct intra-articular composition for inhibiting synovial inflammatory cytokines
Administering directly to an articular cavity of a subject a composition comprising a chondrocyte and a cell into which a gene encoding TGF-β is introduced, wherein the cell is hChonJb#7, and wherein the administration inhibits expression of IL-6, IL-17A, IL-1β, and TNF-α in synovial lavage fluid.
Direct intra-articular injection with engineered TGF-β expressing hChonJb#7
Administering directly to an articular cavity of a subject via an intra-articular injection a composition comprising a chondrocyte and hChonJb#7, wherein the administration inhibits expression of IL-6, IL-17A, IL-1β, and TNF-α in synovial lavage fluid.
Chondrocyte to hChonJb#7 ratio
The method is performed with a chondrocyte to hChonJb#7 ratio ranging from 1:1 to 100:1.
Narrowed chondrocyte to hChonJb#7 ratio
The method is characterized by a specified ratio between chondrocytes and hChonJb#7 ranging from 1:1 to 3:1.
Overall, the independent claims focus on directly administering to an articular cavity a composition containing a chondrocyte and the engineered TGF-β expressing cell hChonJb#7, and on the claimed inhibition of IL-6, IL-17A, IL-1β, and TNF-α expression in synovial lavage fluid. Dependent claim refinements in the partial content further specify chondrocyte-to-hChonJb#7 ratio ranges.
Stated Advantages
Inhibiting expression of IL-6, IL-17A, IL-1β, and TNF-α in synovial lavage fluid in the articular cavity.
Reduced pain and edema after mixed-cell administration.
Decreased synovial cytokines (IL-6, IL-17A, IL-1β, TNF-α) after mixed-cell administration.
Cartilage regeneration findings, including observations consistent with hyaline cartilage and type II collagen.
Documented Applications
Treating rheumatoid arthritis by administering a composition comprising a chondrocyte and hChonJb#7 directly to an articular cavity, including via intra-articular injection.
Using the described mixed-cell administration in preclinical animal models to evaluate reduced pain and edema and decreased synovial cytokines, with reported duration of effects and histological cartilage regeneration findings.
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