resiquimod (STM-416) / SURGE Therap - LARVOL DELTA

Nanovesicles With Mechanically Induced Adjuvanticity for Robust Melanoma Vaccination Toward Tumor-Associated Macrophages. (PubMed, Adv Sci (Weinh)) - "Furthermore, the rigid P-Pm nanovesicle could efficiently co-encapsulate antigenic gp100 peptide and toll-like receptor agonist resiquimod (R848) to form an anti-melanoma vaccine P@Rg-Pm. After intravenously injected, CD8+ T cell infiltration was increased while immune-suppressive cell level of myeloid derived suppressor cells (MDSCs) and regulatory T cells (Tregs) were decreased along with elevated levels of proinflammatory factors including IL-1β, IFN-γ, and IL-12, demonstrating the effective reversal of immunosuppressive TME. Consequently, P@Rg-Pm demonstrates significant antitumor efficacy against B16-F10 melanoma in both therapeutic and prophylactic models without any assistance of other therapies."

Journal • Melanoma • Oncology • Solid Tumor • CD8 • IFNG • IL12A • IL1B

Injectable Thermal-Protective Hydrogel Enables Curative Tumor Ablation via Chemo-Immunomodulation. (PubMed, ACS Appl Mater Interfaces) - "The released MR@CaP (calcium phosphate co-loaded with MIT and R848) nanoparticles disassemble in an acidic environment, delivering mitoxantrone (MIT) and resiquimod (R848) in a dual-responsive manner. With coordinated thermal modulation and programmable drug release, the integrated therapy sterilizes residual tumor cells and achieves complete tumor eradication in 50% of animals. This work establishes a material-driven platform that overcomes thermal safety and immune resistance barriers, offering a translational strategy to enhance procedural safety and long-term efficacy."

Journal • Immunology • Oncology • Solid Tumor • Thermal Injury

Prolonged intratumoral treatment with TLR7/8 agonist R848 regulates the tumor immune microenvironment resulting in enhanced antitumor activity. (PubMed, Cancer Biol Ther) - "Toll-like receptor 7/8 agonists (TLR7/8a), such as resiquimod (R848), are highly potent in activating dendritic cells and thus hold promise for T cell-mediated tumor immunotherapies...Furthermore, the R848 functional concentration assay demonstrated that the micropump prolonged the treatment time of R848 drugs in tumors and reduced the requirement for higher doses, enhancing safety. Taken together, this study provides new insights into TLR7/8a immunotherapy for improved clinical performance, with potential benefits for patients with superficial tumors amenable to prolonged intratumoral infusion via micropump."

Journal • Oncology • CD4 • CD8 • CD86 • IFNG • ITGAX • TNFA

An injectable, dual-crosslinked polypeptide hydrogel encapsulating resiquimod-loaded nanoparticles as a long-lasting immunoprotective tumor vaccine. (PubMed, J Control Release) - "In both prophylactic and post-surgical tumor recurrence models, the gel vaccine successfully induced significant and sustained antigen-specific immune responses, effectively suppressing tumor growth. This study developed an in situ immune cell reprogramming cancer vaccine capable of providing long-term immune protection against tumor growth and recurrence."

Journal • Oncology

A Study of STM-416 Administered to Patients Undergoing TURBT for Recurrent Bladder Cancer (clinicaltrials.gov) - P1/2 | N=75 | Recruiting | Sponsor: SURGE Therapeutics | Trial completion date: Dec 2025 ➔ Aug 2026 | Trial primary completion date: Dec 2025 ➔ May 2026

First-in-human • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Impacts of Prenatal Resiquimod Exposure During Late Gestation on Rat Offspring Development and Behavior. (PubMed, Am J Physiol Regul Integr Comp Physiol) - "Prior studies have shown that prenatal dexamethasone impacts fetal brain development, increases anxiety-like behavior, and dysregulates neuroendocrine and autonomic function in adult rat offspring. The emergence of behavioral changes in adulthood suggests that late-gestation prenatal RQ impacts fetal brain development, revealed by gonadal hormones and metabolic maturation. These changes highlight puberty as critical for exposing the effects of maternal immune activation."

Journal • Preclinical • Mood Disorders • Psychiatry • TLR7

In parallel, the company is advancing two additional intraoperative immunotherapy programs – STM-416 and STM-416p, utilizing the TLR7/8 agonist resiquimod, in bladder cancer and prostate cancer, respectively (Businesswire) - "Both programs are expected to enter Phase 2 clinical trials this year."

New P2 trial • Bladder Cancer • Prostate Cancer

Photoimmunological hydrogel vaccine creates a supportive immune niche to promote antigen cross-presentation cascade and cancer-immunity cycle progression. (PubMed, Acta Pharm Sin B) - "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/[email protected] 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."

Journal • Oncology • CSF2

Pharmacotranscriptomics-based discovery and hydrogel-mediated delivery of drug combinations for potentiated cancer immunotherapy. (PubMed, Sci Bull (Beijing)) - "As a proof of concept, we herein developed an omics-based high-throughput drug screening platform, pharmacotranscriptomic signature enrichment analysis (PSEA), for the prediction of drug combinations of resiquimod (R848) to improve macrophage-mediated cancer immunotherapy. By comparing the critical transcriptional signatures of R848 with chemical perturbation signatures from the LINCS database, PSEA identified mitoxantrone (MIT) as a promising candidate...Transcriptional and flow cytometry results indicated that MIT/R848@Gel remarkably reprogrammed immunosuppressive macrophages toward an antitumor phenotype and effectively activated the antitumor effect of cytotoxic T cells. This study establishes a novel framework integrating omics-driven drug discovery with localized combination therapy for enhanced cancer immunotherapy."

Journal • Oncology • Solid Tumor

Sialic Acid Binding Liposome Nanoparticles for Targeted Bladder Cancer Therapy. (PubMed, ACS Biomater Sci Eng) - "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."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CD4 • CD8

Hyaluronic Acid Hydrogel Implants for Sustained Release of Oxaliplatin and Resiquimod to Prevent Hepatocellular Carcinoma Recurrence Post-Radiofrequency Ablation. (PubMed, Adv Sci (Weinh)) - "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."

Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • CD8

Radioresistance of NSCLC Tumors Is Mediated by Immunosuppressive Cell Populations. Strategies to Sensitize Tumors by Targeting Innate Immunity (IASLC-WCLC 2025) - "Depletion of CSFR1+ cells, Gr1+ cells or the STING/IFNα/β/γ axis with poly(I:C) + resiquimod in radioresistant tumors led to re-sensitization to radiotherapy...Each radioresistant model has their own particular TME, suggesting that, depending on the TME, radioresistance can be mediated by different immune populations. Moreover, targeting the immunosuppressive myeloid population or restoring innate immunity can revert resistance to radiotherapy in NSCLC."

Clinical • IO biomarker • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • IFNA1 • IFNG • PD-1 • STING

Janus micelles formed by blending oppositely charged copolymers encapsulated in a porous hydrogel for subcutaneous glioblastoma treatment models (ACS-Fall 2025) - "Janus micelles, formed by blending oppositely charged alanine-modified (ADF) and ethylenediamine-modified (EDF) Pluronic F127 (1:2 wt.%), encapsulated gemcitabine in the hydrophilic shell and Resiquimod (R848) in the hydrophobic core. In a subcutaneous GBM model, the system reduced tumor volume by 89.5 ± 3.34% and enhanced immune activation, including increased CD80 expression, NF-κB expression, and cytokine production (IFN-γ, TNF-α). This dual-responsive platform addresses challenges in GBM treatment and offers potential as a localized therapeutic strategy."

Brain Cancer • Glioblastoma • Solid Tumor • CD80 • IFNG • TNFA

ROS-responsive resiquimod prodrug nanoparticles for macrophage reprogramming and enhanced immune checkpoint inhibitor therapy in bladder cancer. (PubMed, Biomaterials) - "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."

Checkpoint inhibition • Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CD4 • CD8 • MRC1 • TLR7

Preliminary evaluation of the safety and feasibility of toll-like receptor ligand CB101 combined with hypofractionated radiation therapy in canine head and neck cancer: a pilot study. (PubMed, Vet Oncol) - "Only one grade 1 adverse event was attributable to CB101; all other adverse events were expected radiation therapy side effects. The data obtained from this preliminary study will be used for further investigation into appropriate dosing and timing of intratumoral resiquimod or other TLRs, with eventual escalation into phase II and III clinical trials."

Journal • Head and Neck Cancer • Oncology • Solid Tumor

Maternal Immune Activation Alters Adult Offspring Responses to Stress and Immune Stimulation (ENDO 2025) - "Previous research in mice has used the toll-like receptor 7 (TLR7) agonist, resiquimod, in a maternal immune activation (MIA) model of prenatal stress [Sheng et al., 2024: Brain Behav Immun Integr...The integration of past and current findings underscores the significant impact of prenatal immune stress on neuroendocrine and immune system function after puberty. Ongoing studies of the interactions between autonomic and HPA-associated nuclei, with peripheral pro-inflammatory cytokine challenges, may indicate brain substrates susceptible to developmental programming of immune responses."

Clinical • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry • IL10 • IL17A • IL1B • IL6 • TNFA • ZBTB16

Dual-targeting chemoimmunotherapy co-delivery system based on self-assembly and core-shell structure. (PubMed, Biomed Pharmacother) - "In this study, celastrol (CEL) showing anti-tumor effect through mitochondria-mediated apoptotic pathways, triphenylphosphine (TPP) presenting mitochondria targeting ability, hyaluronic acid (HA) exhibiting cell membrane targeting ability, and immune adjuvants resiquimod (R848) were prepared to form co-delivery system with dual targeting function, which could achieve chemo-immunotherapy for breast cancer. At the low frequency of administration in 4T1 tumor-bearing mouse model, the tumor inhibition rate of H/TCR NPs was 66.5 %, 3-fold higher than paclitaxel injection that was first-line treatment drug of breast cancer in clinic. In summary, this study revealed that co-delivery nanoparticles with dual targeting ability existed combining antitumor effects and presented the potential application in clinic, such as addressing unmet needs in breast cancer treatment or overcoming drug resistance."

Journal • Breast Cancer • Oncology • Solid Tumor

Repurposing oncology drugs to treat autoimmune disease (ASGCT 2025) - "Rituximab is the first monoclonal antibody approved for treating lymphoma, becoming one of the most popular and versatile drugs in clinical application and revenue...In 2014, Blincyto was approved by the FDA for treating acute lymphoma, opening the door to developing T cell engagers (TCE)...TLR 7/8 agonist Resiquimod was applied on the ear of immunodeficient mice after 14 weeks of HSC reconstitution, 3 times a week, with a modeling period of 6 weeks... Developing new drugs requires a significant investment of time and economic costs. The research on drug repurposing has significant advantages over developing new drugs. Humanized SLE models exhibit similar pathological features seen in SLE patients such as high levels of auto-antibodies and pathogenic B cells."

Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Lymphoma • Oncology

Thermosensitive Resiquimod-Loaded Lipid Nanoparticles Promote the Polarization of Tumor-Associated Macrophages to Enhance Bladder Cancer Immunotherapy. (PubMed, ACS Nano) - "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."

IO biomarker • Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CD8

Immunosensitizing effect of TLR agonist combination for the treatment of cold tumors (ITOC 2025) - "These molecules, already used in clinics (e.g., MPLA for cervical cancer, BCG for bladder cancer, and Imiquimod for superficial skin carcinomas), activate immune pathways to enhance anti-tumor immunity. Conclusions Our findings demonstrate that combining OM-174 (TLR4 ligand) and Resiquimod (TLR7 ligand) induces a potent and synergistic immune response, characterized by neutrophil recruitment and a robust type I interferon response ultimately leading to tumor regression. This study underscores the therapeutic potential of combining TLR agonists to overcome the limitations of single-agent therapies and offers a promising avenue for novel cancer immunotherapies, especially for cold tumors."

IO biomarker • Bladder Cancer • Cervical Cancer • Colon Cancer • Colorectal Cancer • Genito-urinary Cancer • Oncology • Skin Cancer • Solid Tumor • CXCL1 • CXCL10 • IFNB1 • MYD88 • TLR4

Intratumoral Injection of R848 and Poly(I:C) Synergistically Promoted Antitumour Immune Responses by Reprogramming Macrophage Polarization and Activating DCs in Lung Cancer. (PubMed, Clin Exp Immunol) - "R848+poly(I:C) synergistically induce M1-like polarization of macrophages, activate DCs, and promote effective antitumour immunity in mice with subcutaneous LLC tumours."

Journal • Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • CD86 • ITGAX

Polyphenol-mediated assembly of toll-like receptor 7/8 agonist nanoparticles for effective tumor immunotherapy. (PubMed, Acta Biomater) - "We here report the polyphenol-mediated assembly of resiquimod (R848, a TLR7/8 agonist) nanoparticles (RTP NPs) to achieve tumor-selective immunotherapy while avoiding systemic adverse effects...The nanoparticles significantly inhibited tumor growth by triggering a potent antitumor immune response, including dendritic cell maturation, macrophage polarization, T-cell infiltration, and cytokine secretion. Moreover, after subcutaneous injection at the tail base, they can elicit immune memory to prevent tumorigenesis."

Journal • Oncology

Iodine-131 radioembolization boosts the immune activation enhanced by icaritin/resiquimod in hepatocellular carcinoma. (PubMed, J Control Release) - "Enhanced anti-tumor efficacy with no relapse was proved in rat orthotopic N1S1 HCC models. These results demonstrated the great potential of this multifunctional embolic agent to treat HCC through transarterial radio-immuno-chemoembolization (TARICE)."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Long-acting intratumoral immunotherapy using multi-drug cocktail eradicates cancer locally and systemically without toxicities (SITC 2024) - "We used up to 5-drug immunotherapeutics combination, consisting of CD40 agonist and CTLA-4 antagonist antibodies, interleukin-12, STING agonist, and resiquimod...Moreover, drug- and tumor-agnosticity allow for broad application across different cancers and drug combination permutations. Ethics Approval Animal experiments were conducted following the Animal Welfare Act and the National Institutes of Health Guide for Care and Use of Laboratory Animals, with protocols approved by the Institutional Animal Care and Use Committee at the Houston Methodist Research Institute."

IO biomarker • Breast Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • CD40 • CTLA4 • IL12A

Rapid Hemostasis Tumor In Situ Hydrogel Vaccines for Colorectal Cancer Chemo-Immunotherapy. (PubMed, ACS Appl Mater Interfaces) - "Here, we have developed a tumor in situ hydrogel vaccine (AH/DA-OR) capable of rapid hemostasis for personalized tumor immunotherapy, composed of dopamine-grafted hyaluronic acid (HA/DA) combined with sodium alginate (ALG), with coloaded oxaliplatin (OXA) and resiquimod (R848). Finally, the hydrogel vaccine effectively activated host immune responses to suppress CT26 colorectal cancer growth in vivo, also exhibiting superior inhibition of untreated tumor growth at distant sites. This strategy of rapid hemostasis of tumor in situ hydrogel vaccine holds significant clinical potential and provides a paradigm for achieving secure and robust immunotherapy."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor