^
    11ms
    Examination of the potential clinical application of 5DEX-0509R, the tumor macrophage-targeting nanomedicine. (PubMed, Cytokine)
    To solve this, we have developed dextran-based TAM targeting activator conjugate (D-TAC) technology which successfully uses tumor-associated macrophages (TAMs) to deliver the TLR7 agonist DSP-0509...In this study, we compared the anti-tumor effects of EIK1001 and 5DEX-0509R, and analyzed its unique immune reaction against tumors to evaluate whether 5DEX-0509R is suitable for further clinical study...We also found that 5DEX-0509R synergistically suppresses tumors with oxaliplatin by changing M2 macrophages that cause oxaliplatin to become resistant to antitumor M1 macrophages. In addition, 5DEX-0509R caused a rapid but not sustained cytokine elevation in both rats and dogs. We believe 5DEX-0509R is worth pursuing for clinical trials.
    Journal
    |
    CD4 (CD4 Molecule)
    |
    oxaliplatin • guretolimod (DSP-0509) • resiquimod sulfate (EIK1001)
    1year
    DSP-0509, a TLR7 agonist, exerted synergistic anti-tumor immunity combined with various immune therapies through modulating diverse immune cells in cancer microenvironment. (PubMed, Front Oncol)
    In summary, our study elucidated the effects of DSP-0509 on immune activity within the tumor microenvironment. These findings provided valuable insights that pave the way for the development of novel combination immunotherapy strategies.
    Journal • Immune cell
    |
    CD8 (cluster of differentiation 8) • TNFA (Tumor Necrosis Factor-Alpha) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • CD4 (CD4 Molecule) • ICOS (Inducible T Cell Costimulator) • IL10 (Interleukin 10) • GZMB (Granzyme B) • PRF1 (Perforin 1)
    |
    CD8 expression • CTLA4 expression
    |
    dubermatinib (TP-0903) • epacadostat (INCB024360) • guretolimod (DSP-0509)
    over1year
    Targeting Tumor-Associated Macrophages with the Immune-Activating Nanomedicine for Achieving Strong Antitumor Activity with Rapid Clearance from the Body. (PubMed, ACS Nano)
    To solve this, we have developed dextran-based TAM targeting activating conjugate (D-TAC) technology, which successfully uses tumor-associated macrophages (TAMs) to deliver the TLR7 agonist DSP-0509...We also demonstrated that the antitumor effect of our best drug candidate 5DEX-0509R is dependent on the abundance of TAMs, which is consistent with their mechanism of action. We believe that 5DEX-0509R generated by D-TAC technology can be a clinically applicable immunotherapy targeting the TLR signaling pathway.
    Journal
    |
    MRC1 (Mannose Receptor C-Type 1)
    |
    guretolimod (DSP-0509)
    over1year
    TLR7 agonist, DSP-0509, with radiation combination therapy enhances anti-tumor activity and modulates T cell dependent immune activation. (PubMed, BMC Immunol)
    These data suggest that TLR7 agonist, DSP-0509, can be a promising concomitant when used in combination with RT by upregulating CTLs activity and gene expression of effector molecules. This combination can be an expecting new radio-immunotherapeutic strategy in clinical trials.
    Journal • Combination therapy • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • GZMB (Granzyme B)
    |
    guretolimod (DSP-0509)
    over1year
    A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile (clinicaltrials.gov)
    P1/2, N=36, Terminated, Sumitomo Pharma America, Inc. | Completed --> Terminated; Sponsor's decision to terminate the development of the program due to changing landscape.
    Trial termination • Combination therapy • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • guretolimod (DSP-0509)
    over2years
    A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile (clinicaltrials.gov)
    P1/2, N=36, Completed, Sumitomo Pharma Oncology, Inc. | Recruiting --> Completed | N=100 --> 36
    Trial completion • Enrollment change • Combination therapy • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • guretolimod (DSP-0509)
    3years
    A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile (clinicaltrials.gov)
    P1/2, N=100, Recruiting, Sumitomo Pharma Oncology, Inc. | Trial completion date: Sep 2025 --> Jan 2023 | Trial primary completion date: Dec 2023 --> Jan 2023
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • guretolimod (DSP-0509)
    over3years
    A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile (clinicaltrials.gov)
    P1/2, N=100, Recruiting, Sumitomo Pharma Oncology, Inc. | Trial completion date: Dec 2023 --> Sep 2025
    Trial completion date • Combination therapy
    |
    PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • guretolimod (DSP-0509)
    4years
    A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile (clinicaltrials.gov)
    P1/2, N=100, Recruiting, Sumitomo Dainippon Pharma Oncology, Inc | Trial completion date: Sep 2021 --> Dec 2023 | Trial primary completion date: Sep 2021 --> Dec 2023
    Clinical • Trial completion date • Trial primary completion date • Combination therapy
    |
    PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • guretolimod (DSP-0509)
    over4years
    A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile (clinicaltrials.gov)
    P1/2, N=100, Recruiting, Sumitomo Dainippon Pharma Oncology, Inc | N=60 --> 100
    Clinical • Enrollment change • Combination therapy
    |
    PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • guretolimod (DSP-0509)