resiquimod (STM-416)

Furthermore, flow cytometry and RNA sequencing confirmed that RFA combined with BI(OXA + R848) significantly enhanced intratumoral dendritic cell activation, promoted the recruitment of CD8⁺ T lymphocytes and NK cells, and induced robust immune memory. This synergistic engagement of the innate-adaptive immune axis underscores its potential to address challenges in both local tumor control and systemic recurrence prevention.

Notably, combination therapy with anti-PD-1 leads to a potent anticancer response in both MB49-bearing mice and patient-derived organoids. This synergy highlights the translational potential of a ROS-responsive prodrug approach for enhancing ICI-based immunotherapies.

Bioinformatics analysis found that R848/DTPA@DSPE-PEG NPs can also induce immune-related gene overexpression of immune signaling pathways. Combined R848/DTPA@DSPE-PEG NPs with PD-1 antibody can significantly enhance antitumor therapeutic effects, reprogram tumor immunosuppressive microenvironment, and prolong the survival time.

R848+poly(I:C) synergistically induce M1-like polarization of macrophages, activate DCs, and promote effective antitumour immunity in mice with subcutaneous LLC tumours.

NPS in combination with the adjuvant and TLR agonist, resiquimod (RES), was the optimal treatment regimen for both eliminating a primary Pan02 tumor as well as inhibiting growth of a Pan02 cell rechallenge tumor...NPS plus RES was the most effective at both eliminating a primary tumor and inhibiting a rechallenge tumor. NPS treatment followed by injection of aOX40 was the most effective at inhibiting the growth of an untreated abscopal tumor.

P1/2, N=75, Recruiting, SURGE Therapeutics | Trial completion date: Sep 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Dec 2025

The goal of this study was to determine sex-dependent aspects of MIA using a TLR7/8 agonist, Resiquimod (RQ), on neurodevelopment...This study provides support for sex-dependent influences of fetal antecedents for altered brain development and behavioral outputs that could be indicative of increased susceptibility for adult disorders through immune mechanisms. Future studies are needed to determine neural cellular and molecular mechanisms for such programming effects.

While no significant alterations were observed in T cell numbers (CD8, CD4 or Treg), TAM-reprogramming in treated mice was confirmed by the relative decrease of interstitial versus alveolar macrophages, having higher CD86 expression but lower CD206 and Arg1 expression in the same cells, in treated mice. Mannose-HA-protamine-NCs loaded with poly(I:C)+R848 successfully reprogram TAMs in vivo, and reduce tumor progression and metastasis spread in mouse tumors.

P1/2, N=75, Recruiting, SURGE Therapeutics | Not yet recruiting --> Recruiting | Initiation date: Mar 2023 --> Jun 2023

Resiquimod, a TLR7/8 agonist, and axitinib, a vascular endothelial growth factor tyrosine kinase inhibitor, were chosen as anti-cancer drugs. In summary, TransCon Hydrogel technology allows localized sustained-release drug delivery for cancer therapy enabling high local drug concentrations while at the same time ensuring low systemic drug exposure over weeks with a single injection, which may improve the therapeutic index and improve efficacy, while minimizing systemic adverse events. A hydrogel prodrug of resiquimod, TransCon TLR7/8 agonist, is currently being investigated in clinical trials of patients with solid tumors (NCT04799054).

In conclusion, our work clearly demonstrates that pIC+R848 are an effective treatment for PDAC when injected intratumorally and that this activity strongly relies on IFN-γ and adaptive immunity. Further investigations are ongoing to assess their potential in orthotopic models using different routes of administration, in a setting closer to the real clinical situation.