resiquimod (STM-416)

The model antigen ovalbumin (OVA) and toll-like receptor 7/8 agonist resiquimod (R848) were incorporated into photothermal copper sulfide nanoparticles (CuS) to construct the nanovaccine CRPO, which was subsequently encapsulated with the granulocyte-macrophage colony-stimulating factor (GM-CSF) in sodium alginate (ALG) to form the hydrogel vaccine CRPO/G@ALG...In 4T1 tumor-bearing mice, CRPO/G@ALG effectively suppressed primary and distant tumor growth and markedly reduced lung metastasis. Collectively, our findings illustrate the transformative potential of integrating ICD induction, DC recruitment, and hydrogel delivery systems, offering new avenues to advance therapeutic tumor vaccine applications.

We fabricated tumor-targeting liposome-chitosan-CPBA (LPCB) nanoparticles coloaded with doxorubicin (Dox), a chemotherapeutic agent, and resiquimod (R848), a toll-like receptor (TLR) 7/8 agonist that stimulates antitumor immunity...Flow cytometric analysis of tumor and spleen samples further showed robust activation of Natural Killer (NK) cells, CD4+ T cells, and CD8+ T cell effector functions. Combined results demonstrate that sialic acid targeting LPCBDR nanoparticles offers a promising drug delivery platform for bladder cancer therapy.

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