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Tandem CAR-T cells targeting CLDN18.2 and NKG2DL for treatment of gastric cancer. (Available On Demand; 18) - Apr 28, 2022 - Abstract #ASCO2022ASCO_1870; KD-496 CAR-T cells potently respond to GC and more efficient tumor elimination than single CAR such as KD-025 and KD-182 CAR-T cells in PDX model with no obvious safety issue. The results support future clinical trial of KD-496 CAR in patients with GC, where the need for effective treatment is great.
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Journal: KD025 Shifts Pulmonary Endothelial Cell Bioenergetics and Decreases Baseline Lung Permeability. (Pubmed Central) - Nov 25, 2020 We tested endothelial permeability in vivo using Evans Blue dye in the bleomycin pulmonary fibrosis model...ROCK2 knockdown had no effect on PMVEC metabolism, pH and migration, but it increased non-apoptotic caspase-3 activity. Together, we report that KD025 promotes oxidative phosphorylation, decreases glycolysis, intracellular pH and migration, and strengthens pulmonary barrier integrity in a ROCK2 independent manner.
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Clinical, Journal: KD025, an anti-adipocyte differentiation drug, enhances the efficacy of conventional chemotherapeutic drugs in ABCG2-overexpressing leukemia cells. (Pubmed Central) - Oct 26, 2020 KD025 (SLx-2119) is a novel Rho-associated protein kinase 2-selective inhibitor, which has been shown to inhibit adipogenesis in human adipose-derived stem cells and restore impaired immune homeostasis in autoimmunity therapy...Moreover, KD025 significantly inhibited the efflux of [H]-mitoxantrone and hence accumulated higher levels of [H]-mitoxantrone in HL60/ABCG2 cells...Taken together, KD025 can sensitize conventional antineoplastic drugs in ABCG2-overexpressing leukemia cells by blocking the pump function of ABCG2 protein. The present findings may provide a novel and useful combinational therapeutic strategy of KD025 and antineoplastic drugs for leukemia patients with ABCG2-mediated MDR.
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Enrollment change, Trial completion date, Trial initiation date, Trial withdrawal, Trial primary completion date, CAR T-Cell Therapy: NKG2D-based CAR T-cells Immunotherapy for Patient With r/r NKG2DL+ Solid Tumors (clinicaltrials.gov) - Oct 22, 2020 P1, N=0, Withdrawn, The present findings may provide a novel and useful combinational therapeutic strategy of KD025 and antineoplastic drugs for leukemia patients with ABCG2-mediated MDR. N=10 --> 0 | Trial completion date: Dec 2023 --> Oct 2020 | Initiation date: Oct 2020 --> Mar 2020 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2022 --> Oct 2020
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Preclinical, Journal: ROCK2 inhibition enhances the thermogenic program in white and brown fat tissue in mice. (Pubmed Central) - Jul 9, 2020 Treatment with a selective ROCK2 inhibitor, KD025, to inhibit ROCK2 activity in differentiated SV cells reproduced the pro-beige phenotype of ROCK2 SV cells. In conclusion, ROCK2 activity-mediated actin cytoskeleton dynamics contribute to the inhibition of beige adipogenesis in WAT, and also promotes age-related and diet-induced fat mass gain and insulin resistance.
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Journal: KD025 (SLx-2119) suppresses Adipogenesis at Intermediate Stage in Human Adipose-derived Stem Cells. (Pubmed Central) - Mar 26, 2020 In addition, we observed that other ROCK inhibitors such as Y-27632, fasudil, and H-1152P did not suppress but promoted adipocyte differentiation. These results indicate that KD025 suppresses adipocyte differentiation by modulation of key factors activated at the intermediate stage of differentiation, and not by inhibition of ROCK2.
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