vadimezan (ASA404) / Antisoma - LARVOL DELTA

Effect of Corona Block Structure on Telodendrimer Micelles: Probing Exchange Kinetics by Fluorescence Spectroscopy. (PubMed, Biomacromolecules) - "Telodendrimer micelles with low critical micelle concentrations (CMCs) were synthesized using a hydrophilic poly(sarcosine) (PSar) block and a lysine-based dendritic block carrying four stably conjugated Vadimezan...Slower unimer re-entry was observed for larger, sterically hindered unimers. The study suggests that hydrophilic block size and topology are equally important in the design criteria as the hydrophobic portion for stability and CMC alone is insufficient to predict micelle behavior in complex biological media."

Journal

Anti-Triggering Receptor Expressed on Myeloid Cells 2-Conjugated Nanovesicles Loaded Vadimezan Reprogram Tumor-Associated Macrophages to Combat Recurrent Lung Cancer. (PubMed, ACS Nano) - "Simultaneously, anti-TREM2 effectively repolarized TAMs into M1-type macrophages, thereby reversing immunosuppressive TME together with a Vad-activated STING pathway, which promoted the maturation of dendritic cells and enhanced the infiltration of cytotoxic T lymphocytes. Therefore, this study highlighted the FP/Vad@CC-aT2-mediated cascade immune response for suppressing lung cancer recurrence that involves ferroptosis potentiation, TAM repolarization, and STING pathway activation."

Journal • Lung Cancer • Oncology • Solid Tumor • CGAS • STING

Acoustically activated nanoplatforms achieve tumor regression by exacerbating tumor hypoxia. (PubMed, J Cancer Res Ther) - "The DIS NPs exhibit a promising approach for hypoxia-exacerbated cancer starvation therapy, providing a potential new avenue for cancer treatment with demonstrated efficacy and biocompatibility."

Journal • Oncology

Implantable Biophotonic Device for Wirelessly Cancer Real-Time Monitoring and Modulable Treatment. (PubMed, Adv Sci (Weinh)) - "Furthermore, this device can also evaluate the therapeutic progression of chemotherapy drugs like vadimezan, which reduces sO2 levels by disrupting tumor angiogenesis...It operates via wireless power and data transmission without disrupting normal physiological activities. Hence, the biophotonic device is capable of concurrently achieving precise tumor discrimination, modulable in situ treatments, and real-time progression monitoring, enabling the evaluation and optimization of therapeutic efficacy."

Journal • Oncology

STING-activating layered double hydroxide nano-adjuvants for enhanced cancer immunotherapy. (PubMed, Biomaterials) - "Additionally, combining MLMF with the vascular disrupting agent Vadimezan disrupted the tumor's central region, typically resistant to immune cell infiltration, further extending survival in tumor-bearing mice. This innovative strategy may show great potential for improving cancer immunotherapy and offers hope for more effective treatments in the future."

Journal • Oncology • STING

A stimuli-responsive immunostimulant to activate chemo-immunotherapeutic effects by inducing DNA damage and STING activation. (PubMed, J Colloid Interface Sci) - "The MV@Lip system encapsulates the chemotherapeutic agent mitoxantrone (Mit) and the STING agonist vadimezan (Vad) within a redox-responsive liposomal carrier. This concerted action facilitates the infiltration and activation of natural killer (NK) cells and T lymphocytes in the tumor microenvironment, ultimately leading to the suppression of both primary and metastatic tumors. These findings provide a compelling basis for advancing chemotherapeutic combinations as immune-stimulating strategies in the treatment of metastatic malignancies."

Journal • Oncology • STING

Cabozantinib-Induced Mitochondrial Activation of the cGAS-STING Pathway Enhances the Antitumor Immunity in Experimental Hepatocellular Carcinoma (LCS 2025) - "In vivo, the anti-tumor efficacy of cabozantinib and/or vadimezan, a STING agonist, was evaluated using a subcutaneous Hepa1-6 injection mouse model... Cabozantinib induces mtDNA-dependent cell death via cGAS-STING signalling in hepatoma cells. STING stimulation enhanced cabozantinib efficacy. Our results, emphasize the role of the cGAS-STING axis in TKI therapies and its agonism as a promising strategy for HCC treatment."

IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • CD8 • CGAS • GZMB

A responsive cocktail nano-strategy breaking the immune excluded state enhances immunotherapy for triple negative breast cancer. (PubMed, Nanoscale) - "Herein, we fabricated a smart-responsive nanosystem (B&V@ZB-MCL) by integrating the extracellular matrix (ECM)-degrading drug losartan with a STING agonist (Vadimezan, abbreviated to Vad) and a PD-L1 inhibitor (BMS-1). The released Vad and damaged tumor DNA activated immune responses through the cGAS-STING pathway, while the elevated expression level of PD-L1 promoted the anti-tumor effect of BMS-1. Significant degradation of collagen fibers, restoration of immune effector cells, and lower tumor volume were observed in this integrated triple drug sequential therapy, which provides a promising prospect for TNBC treatment."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CGAS • STING

Multifunctional nanoparticles potentiate in-situ tumor vaccines via reversing insufficient Photothermal therapy by disrupting tumor vasculature. (PubMed, J Control Release) - "To overcome these limitations, we developed multi-functional nanoparticles (VI@Gd-NPs) that integrate a tumor vasculature-specific disrupting agent (Vadimezan, Phase III clinical drug), a photosensitizer (Indocyanine Green, ICG), and a magnetic resonance imaging contrast agent (Gadolinium, Gd) through chemical self-assembly...Moreover, depleting CD8+ T cells reverses these therapeutic benefits, highlighting the critical role of adaptive T cell immunity. Therefore, the VI@Gd-NPs treatment holds great potential for reigniting the in-situ tumor vaccine of photothermal therapy."

Journal • Oncology • CD8

Augmenting Post-Surgical Tumor Immune Response and Recurrence Prevention via Nanoparticle-Assisted Targeted Drug Delivery (IASLC-WCLC 2024) - "Methods : FP/Vad@CC-aT2, a biomimetic nanoparticle system containing FePt and Vadimezan, was prepared via extrusion and conjugated with anti-Trem2 antibodies...Conclusions : The study developed FP/Vad@CC-aT2, a targeted delivery system with good biocompatibility and significant antitumor effects. It was found to promote immune remodeling, induce immunogenic cell death, and alter immune cell composition in post-surgical relapse mouse models, suggesting its potential in preventing postoperative relapse and providing a basis for clinical applications."

IO biomarker • Lung Cancer • Oncology • Solid Tumor • CD8 • HMGB1 • STING

Identification of critical genes and metabolic pathways in rheumatoid arthritis and osteoporosis toward drug repurposing. (PubMed, Comput Biol Med) - "The results of the present study can provide novel insights into the pathogenesis and treatment of RA and OP."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Osteoporosis • Rheumatoid Arthritis • Rheumatology • CCL2 • HIF1A • IL10 • IL1B • IL6 • MMP9 • STAT3 • TGFB1 • TP53

Cabozantinib induces mtDNA-dependent cytotoxicity through cGas-STING signaling in experimental hepatocellular carcinoma (EASL-ILC 2024) - "Previous studies demonstrated that TKI inhibitors such as sorafenib and regorafenib induce mitochondrial damage during cancer treatment...Importantly, while blockage of this pathway (H-151) partially diminished cabozantinib cytotoxicity, vadimezan induction of cGas-STING potentiated the anti-tumor effect in vitro and in a Hepa1-6 3D spheroid model. Cabozantinib-induced mtDNA leakage to the cytosol induces ISGs signaling by activating the cGas-STING pathway in hepatoma cells. Our results reveal mitochondrial damage and the mtDNA-cGas-STING axis as compelling targets in antitumor efficacy with a potential role in immunological responses."

Gastrointestinal Cancer • Hepatocellular Cancer • Immunology • Oncology • Solid Tumor • CGAS • STING

Integrated anti-vascular and immune-chemotherapy for colorectal carcinoma using a pH-responsive polymeric delivery system. (PubMed, J Control Release) - "Herein, we designed a pH-responsive polymer to efficiently encapsulate a stimulator of interferon genes (STING) agonist (5,6- dimethylxanthenone-4-acetic acid, termed ASA404) and a common clinically used chemotherapeutic agent (1-hexylcarbamoyl-5-fluorouracil, termed HCFU). Histological analysis of the tumor micro-vessel density and enzyme-linked immunosorbent assay (ELISA) tests indicated that the system increased TNF-α and IFN-β levels in serum. Therefore, this research introduces a pH-responsive polymer-based theranostic platform with great potential for immune-chemotherapeutic and anti-vascular combination therapy of CRC."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • IFNB1 • STING • TNFA

Engineering cell membrane nanoparticlesenhance immunotherapy and radiodynamic therapy for lung adenocarcinoma by promoting cGAS-STING and ferroptosis (AACR 2024) - "The vehicle utilized lung adenocarcinoma cell membranes as the outer shell and encapsulated iron-platinum nanoparticles and STING agonist Vadimezan... This study developed a targeted drug delivery strategy, FP/Vad@CC-aT2, to improve the tumor microenvironment (TME). We conducted preliminary experiments in vitro and in vivo to validate its physicochemical properties and tumor inhibitory effects, including the induction of ferroptosis. We assessed its safety in mouse and obtained initial evidence of FP/Vad@CC-aT2's ability to remodel the subtypes of macrophage.Moving forward, we will validate its therapeutic and impact on the TME after surgical procedures."

Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MRC1 • STING

Computational study of small molecules with open and closed states of human STING: Effects on protein conformations and binding free energies (ACS-Fall 2023) - "An antitumor agent called DMXAA (5,6-dimethylxanthenone-4-acetic acid, Vadimezan), which mimics the structure of cGAMP, was found to be very effective in murine models...The information gathered from this research further clarifies previous studies and proposed hypotheses, increasing our knowledge of the STING signaling pathway. They should assist in further designing the ligands as STING modulators and provide a theoretical basis for molecular-level understandings of their binding process to the STING proteins."

Oncology • STING

Radiation and STING activation limit tumor development and modulate the immune environment via distinct mechanisms (AACR 2023) - "In this study, we examined the effect of radiation and the STING agonist, DMXAA (Vadimezan), on the development of urethane-induced lung cancer.A/J mice were treated with urethane (i.p.) to induce the development of lung tumors...The different outcomes of RT and DMXAA on tumor growth may be driven by their distinctive mechanism of action on immune responses and capacities to form TLSs. These findings may have future implications for strategies for the early treatment of lung and other cancers, and they suggest that immune responses, including modulation of the STING pathway, may be an important aspect of early tumor development that could be targeted therapeutically."

Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • CXCL13 • STING • TNFA

Nanodroplet-enhanced sonodynamic therapy potentiates immune checkpoint blockade for systemic suppression of triple-negative breast cancer. (PubMed, Acta Biomater) - "The synthesized nanodroplet consisted of a O-filled Perfluorohexane (PFH) core and a lipid membrane carrying sonosensitizer IR-780 and STING agonist Vadimezan (DMXAAs)...However, the hypoxic tumor microenvironment severely restricts the therapeutic efficiency of SDT, wherein, oxygen is indispensable in the process of ROS generation. Here, we report an O-filled nanodroplet-enhanced sonodynamic therapy that significantly potentiated immune checkpoint blockade for systemic suppression of TNBC."

Checkpoint inhibition • Journal • Breast Cancer • Immune Modulation • Immunology • Inflammation • Oncology • Solid Tumor • Triple Negative Breast Cancer

Lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein for combinational immunochemotherapy of metastatic triple-negative breast cancer. (PubMed, Acta Pharm Sin B) - "The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1. This study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC."

Journal • Breast Cancer • Immune Modulation • Immunology • Inflammation • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1 • STING

Phytochemistry, biological activities and in silico molecular docking studies of Oxalis pes-caprae L. compounds against SARS-CoV-2. (PubMed, J King Saud Univ Sci) - "Using molecular docking, it was found that Caeruleanone A, 2',4'-Dihydroxy-2″-(1-hydroxy-1-methylethyl) dihydrofuro [2,3-h] flavanone and Vadimezan demonstrated best affinity with the investigated SARS CoV-2 Mpro protein. This work provide justification about this plant as a source of effective phytochemicals and their potential against microbes could lead to development of biosafe drugs for the welfare of human being. In future, different in vitro and in vivo biological studies can be performed to further investigate its biomedical potentials."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The Potential of STING Agonists Is Explored in Cancer (Targeted Oncology) - "Although preclinical data are exciting, clini- cal results with STING agonists remain elu- sive. 'Every single company has preclinical modeling to indicate their version of this is the best,' said Luke...'We may need to be targeting other antigen-presenting populations, such as monocytes or myeloid cells,' said Luke."

Media quote

Synthesis and Properties of α-Mangostin and Vadimezan Conjugates with Glucoheptoamidated and Biotinylated 3rd Generation Poly(amidoamine) Dendrimer, and Conjugation Effect on Their Anticancer and Anti-Nematode Activities. (PubMed, Pharmaceutics) - "This effect was significantly enhanced after conjugation of the drug with the dendrimer via the amide, but not the ester bond, with G3 inhibiting the proliferation of SCC-15 and U-118 MG cells at concentrations ≥4 and ≥12 μM, respectively, without a visible effect in normal BJ cells. Thus, the drug delivery system based on the PAMAM G3 dendrimer containing amide bonds, partially-blocked amino groups on the surface, larger particle diameter and higher zeta potential can be a useful tool to improve the biological properties of transported drug molecules."

Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • Squamous Cell Carcinoma

Highlight Therapeutics: BO-112 published in JITC (GlobeNewswire) - “BO-112 and DMXAA when co-injected in one of the lesions of mice bearing concomitant bilateral tumors frequently achieved complete local and distant antitumor efficacy. Synergistic effects were contingent on CD8 T cell lymphocytes and dependent on conventional type 1 dendritic cells, responsiveness to type I IFN and STING function in the tumor-bearing host. Efficacy was preserved even if BO-112 and DMXAA were injected in separate lesions in a manner able to control another untreated third-party tumor. Efficacy could be further enhanced on concurrent PD-1 blockade….Initiation of a pivotal Phase 3 study in 2nd-line melanoma is planned in 2022 following discussions with regulatory agencies in the US and Europe…Initial data from a sponsor-initiated Phase 1B trial by UCLA evaluating BO-112 + pembrolizumab in anti-PD1 resistant hepatocellular carcinoma currently recruiting patients is expected in 2022”

New P3 trial • P1 data • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Melanoma • Oncology • Skin Cancer

Flavonoid-Inspired Vascular Disrupting Agents: Exploring Flavone-8-Acetic Acid and Derivatives in the New Century. (PubMed, Molecules) - "Consequently, in the last decade a renewal of interest for these flavonoid-based structures was noticed, and novel derivatives have been synthesised and evaluated for a deeper understanding of the molecular features needed for affecting human cells. Undoubtedly, these natural-derived molecules deserve further investigation and still appear attractive in an anticancer perspective."

Journal • Review • Oncology • STING

Disrupting tumour vasculature and recruitment of aPDL1-loaded platelets control tumour metastasis. (PubMed, Nat Commun) - "Briefly, we have developed a combination in which Vadimezan disrupts tumour blood vessels of tumour metastases and facilitates the recruitment and activation of adoptively transferred aPDL1-conjugated platelets. In situ activated platelets generate aPDL1-decorated platelet-derived microparticles (PMP) that diffuse within the tumour and elicit immune responses. The proposed combination increases 10-fold aPDL1 antibody accumulation in lung metastases as compared to the intravenous administration of the antibody and enhances the magnitude of immune responses leading to improved antitumour effects."

Journal • Oncology

Co-Administration of Vadimezan and Recombinant Coagulase-NGR Inhibits Growth of Melanoma Tumor in Mice. (PubMed, Adv Pharm Bull) - "The tCoa-NGR induce thrombosis which reduces blood flow in the peripheral tumor region. And combined with the action of DMXAA, which target inner tumor mass, growth and proliferation of melanoma tumors can be significantly suppressed."

Journal • Preclinical • Cardiovascular • Hematological Disorders • Melanoma • Oncology • Solid Tumor • Thrombosis