^
4ms
Dual Adjuvant-Loaded Peptide Antigen Self-Assembly Potentiates Dendritic Cell-Mediated Tumor Immunotherapy. (PubMed, Adv Sci (Weinh))
R848, TLR 7/8 agonist, and SD-208, TGF-beta receptor1 kinase inhibitor, are coencapsulated into the nanoassembly as potent adjuvants to boost DC maturation and enhance antigen presentation...Furthermore, DA-L-DSA exhibits a remarkable synergistic effect in the combination therapy with immune checkpoint inhibitors alleviating immunosuppressive tumor microenvironment. Taken together, these findings suggest DA-L-DSA as a promising immuno-therapeutic platform that could be applicable to diverse intractable cancers.
Journal
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BIRC5 (Baculoviral IAP repeat containing 5) • TGFB1 (Transforming Growth Factor Beta 1)
|
SD 208
11ms
Engineering TGF-β inhibitor-encapsulated macrophage-inspired multi-functional nanoparticles for combination cancer immunotherapy. (PubMed, Biomater Res)
Collectively, responsiveness to immune checkpoint inhibitors was considerably enhanced and a robust anti-cancer effect was demonstrated with the combination treatment of M[Formula: see text]-SDNPs and anti-PD-1 antibody. This suggests a promising direction for future therapeutic strategies, utilizing bio-inspired nanotechnology to improve the efficacy of cancer immunotherapy.
Journal
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TGFB1 (Transforming Growth Factor Beta 1)
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SD 208
12ms
TGF-β Inhibitor SD-208 Enhances the Anti-Tumor Efficacy of CD19 CAR-T Cells through a Reduction of CAR-Treg in Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (ASH 2023)
Inhibition of TGF-β by TGF-β/SMAD inhibitor SD-208 inhibit the proliferation of Treg in PBMCs of r/r B-ALL patients. TGF-β inhibitor SD-208 might improve the anti-tumor ability of CD19 CAR-T cells via decreasing Treg and CAR-Treg in r/r B-ALL.
Clinical • CAR T-Cell Therapy
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CD8 (cluster of differentiation 8) • IL2RA (Interleukin 2 receptor, alpha) • CD4 (CD4 Molecule) • IL7R (Interleukin 7 Receptor) • GZMB (Granzyme B) • TGFB1 (Transforming Growth Factor Beta 1)
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SD 208
over1year
Dissolvable Self-locking Microneedle Patches Integrated with Immunomodulators for Cancer Immunotherapy. (PubMed, Adv Mater)
(TGF-?) inhibitor that suppresses the proliferation and metastasis of tumors, and anti-PD-L1 (?PD-L1 Ab), an immune checkpoint inhibitor that induces T cell-mediated tumor cell death, into self-locking MNs and compared with intratumoral injection. Evaluation of (?PD-L1 Ab)/SD-208 delivery effectiveness in B16F10 melanoma-bearing mice model confirmed significantly improved dose efficacy of self-locking MNs compared with intratumoral injection.
Journal • Immunomodulating
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TGFB1 (Transforming Growth Factor Beta 1)
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SD 208
almost3years
Exosome-Mediated Delivery of Transforming Growth Factor-β Receptor 1 Kinase Inhibitors and Toll-Like Receptor 7/8 Agonists for Combination Therapy of Tumors. (PubMed, Acta Biomater)
We first demonstrated that combined treatment with SD-208 and R848 can be a convincing strategy to circumvent tumor growth in vivo using serum-derived exosomes as promising carriers. Therefore, we believe this manuscript would be of great interest to the biomaterial communities especially who are studying immunotherapy.
Journal • Combination therapy
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TGFB1 (Transforming Growth Factor Beta 1)
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SD 208
over3years
A mesenchymal-like subpopulation in non-neuroendocrine small cell lung cancer contributes to metastasis. (PubMed, J Genet Genomics)
Importantly, inhibition of the TGF-β signaling through ectopic expression of dominant-negative Tgfbr2 (Tgfbr2-DN) or treatment with Tgfbr1 inhibitor SD-208 consistently abrogated tumor metastasis in nude mouse allograft assays. Moreover, genetic deletion of Tgfbr2 or Smad4, the key components of the TGF-β signaling pathway, dramatically attenuated SCLC metastasis in the RP autochthonous mouse model. Collectively, our results uncover the high heterogeneity in non-NE SCLC cells and highlight an important role of TGF-β signaling in promoting SCLC metastasis.
Clinical • Journal
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TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • SMAD4 (SMAD family member 4) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • TGFB1 (Transforming Growth Factor Beta 1)
|
SD 208
4years
Structure-Based Virtual Screening, Molecular Dynamics and Binding Free Energy Calculations of Hit Candidates as ALK-5 Inhibitors. (PubMed, Molecules)
ALK-5 inhibitors, such as SB505154, GW6604, SD208, and LY2157299, have recently been reported to inhibit ALK-5 autophosphorylation and induce the transcription of matrix genes. From a lead-like subset of purchasable compounds, five molecules were identified as putative ALK-5 inhibitors. In addition, molecular dynamics and binding free energy calculations combined with pharmacokinetics and toxicity profiling demonstrated the suitability of these compounds to be further investigated as novel ALK-5 inhibitors.
Journal
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ALK (Anaplastic lymphoma kinase)
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galunisertib (LY2157299) • SD 093 • SD 208
4years
TGFβ inhibition stimulates collagen maturation to enhance bone repair and fracture resistance in a murine myeloma model. (PubMed, J Bone Miner Res)
Using in vivo μCT we show substantial and rapid bone lesion repair (and prevention) driven by SD-208 (TGFβ receptor I kinase inhibitor) and chemotherapy (bortezomib and lenalidomide) in mice with human U266-GFP-luc myeloma. We also discovered that SD-208 promoted osteoblastic differentiation (and overcame the TGF?-induced block in osteoblastogenesis) in myeloma patient bone marrow stromal cells in vitro, comparable to normal donors. The improved bone quality and fracture-resistance with SD-208 provides incentive for clinical translation to improve myeloma patient quality of life by reducing fracture risk and fatality.
Preclinical • Journal
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VEGFA (Vascular endothelial growth factor A)
|
lenalidomide • bortezomib • SD 093 • SD 208
over4years
Inhibition of TGF-β-receptor signaling augments the antitumor function of ROR1-specific CAR T-cells against triple-negative breast cancer. (PubMed, J Immunother Cancer)
We demonstrate the TGF-β suppresses the antitumor function of ROR1-CAR T-cells against TNBC in preclinical models. Our study supports the continued preclinical development and the clinical evaluation of combination treatments that shield CAR T-cells from TGF-β, as exemplified by the TGF-β-receptor kinase inhibitor SD-208 in this study.
Journal • CAR T-Cell Therapy • PD(L)-1 Biomarker
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CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • SMAD4 (SMAD family member 4)
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PD-1 expression
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SD 093 • SD 208