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

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

Minimally Invasive Injectable Gel for Local Immunotherapy of Liver and Gastric Cancer. (PubMed, Adv Sci (Weinh)) - "The loaded oxaliplatin (OxP) and resiquimod (R848) can be released constantly over two weeks and resulted in over 75% cure rate in orthotopic mouse gastric and liver cancer model. Collectively, a concept of minimally invasive local immunotherapy is proposed and MIGel is designed for local intraperitoneal cancer immunotherapy through minimally invasive surgery, with good clinical translation potential."

Journal • Gastric Cancer • Gastrointestinal Cancer • Hepatology • Liver Cancer • Oncology • Peritoneal Cancer • Solid Tumor

Nano-Pulse Stimulation Treatment Inhibits Pan02 Murine Pancreatic Tumor Growth and Induces a Long-Term Adaptive Immune Response with Abscopal Effects When Combined with Immune-Enhancing Agents. (PubMed, Bioelectricity) - "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."

Journal • Preclinical • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CD8

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: Sep 2024 ➔ Dec 2025 | Trial primary completion date: Jun 2024 ➔ Dec 2025

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

Design and Synthesis of Polyphenolic Imidazo[4,5-c]quinoline Derivatives to Modulate Toll Like Receptor-7 Agonistic Activity and Adjuvanticity. (PubMed, ACS Pharmacol Transl Sci) - "TLR-7/8 agonists are a well-known class of vaccine adjuvants, with a leading example now included in Covaxin, a licensed human COVID-19 vaccine. Even though compound 12d exhibited low TLR7 activity (EC50 = 5.13 μM in TLR7), it demonstrated superior adjuvant results, which may be attributed to its enhanced alum adsorption capability as compared with BBIQ and resiquimod. Alum-adsorbed polyphenolic TLR7 agonists thereby represent promising combination adjuvants resulting in a balanced Th1/Th2 immune response."

Journal • Hepatology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

Maternal immune activation with toll-like receptor 7 agonist during mid-gestation alters juvenile and adult developmental milestones and behavior. (PubMed, J Neuroendocrinol) - "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."

Journal • Autism Spectrum Disorder • CNS Disorders • Depression • Genetic Disorders • Infectious Disease • Major Depressive Disorder • Mental Retardation • Mood Disorders • Oncology • Psychiatry • Schizophrenia • IL10 • IL17A • IL6 • TNFA

The Remarkable Anti-Breast Cancer Efficacy and Anti-Metastasis by Multifunctional Nanoparticles Co-Loading Squamocin, R848 and IR 780. (PubMed, Int J Nanomedicine) - "Resiquimod (R848) or ginsenoside Rh2 was co-encapsulated in the nanoparticles to remold the immunosuppressive tumor microenvironment, and IR780 was coloaded as a photosensitizer to realize photothermal therapy...Both multifunctional nanoparticles, Squ-Rh2-IR780 nanoparticles and Squ-R848-IR780 nanoparticles, demonstrated even better therapeutic efficacy, with tumor inhibition rates of 90.02% and 97.28%, pulmonary metastasis inhibition rates of 95.42% and 98.09, and mean survival times of 46 days and 52 days, respectively. The multifunctional nanoparticles coloaded with squamocin, R848 and IR 780 achieved extraordinary therapeutic efficacy and excellent antimetastasis activity and are thus promising in the future treatment of breast tumors and probably other tumors."

Journal • Breast Cancer • Oncology • Solid Tumor

Maternal Immune Activation During Mid-Gestation Leads to Impaired Neuroendocrine Stress Response and Blood-Brain Barrier Integrity in a Sex-Dependent Manner (ENDO 2024) - " Timed-pregnant female mice were administered the TLR7 agonist Resiquimod (RQ) or vehicle saline on embryonic day 12.5... This study provides support for sex-dependent influences of fetal immune antecedents on brain development and adult neuroendocrine function that could indicate a locus for increased susceptibility to adult neuropsychiatric disorders. While the current experiments found significant post-pubertal changes selectively in adult PVN, ongoing studies are examining whether these effects are evident prior to puberty. Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation."

CNS Disorders • Mental Retardation • Mood Disorders • Psychiatry • GFAP

ROS-responsive thermosensitive polypeptide hydrogels for localized drug delivery and improved tumor chemoimmunotherapy. (PubMed, Biomater Sci) - "In this study, we developed a ROS-responsive thermosensitive poly(ethylene glycol)-polypeptide hydrogel loaded with a chemotherapeutic drug, doxorubicin (Dox), an antiviral imidazoquinoline, resiquimod (R848), and antibody targeting programmed cell death protein 1 (aPD-1) for local chemoimmunotherapy. In the postoperative model, the Dox/R848/aPD-1 co-loaded hydrogel exhibited enhanced tumor recurrence prevention and long-term immune memory effects. Thus, the hydrogel-based local chemoimmunotherapy system demonstrates potential for effective anti-tumor treatment and suppression of tumor recurrence."

Journal • Melanoma • Oncology • Solid Tumor

Invited talk: Magnetic microrobots for macrophage transport, activation, and imaging (ACS-Sp 2024) - "First, we show magnetic backpacks fabricated using soft lithography can encapsulate superparamagnetic iron oxide nanoparticles (SPIONs) and resiquimod, a small molecule drug that drives the phenotype of macrophages towards an antitumor phenotype... The combination of sustained macrophage polarization, magnetic trapping, and high-resolution monitoring highlights the potential of magnetic helices and discs to improve the performance of ACTs for cancer immunotherapy."

Oncology • IL12A

Polymeric nanocapsules loaded with poly(I:C) and resiquimod to reprogram tumor-associated macrophages for the treatment of solid tumors. (PubMed, Front Immunol) - "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."

IO biomarker • Journal • Fibrosarcoma • Lung Cancer • Oncology • Sarcoma • Solid Tumor • CD4 • CD8 • CD86 • CXCL10 • MRC1