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    DRUG CLASS:

    CAIX-targeted antibody-drug conjugate

    Related drugs:
    3ms
    Tumor targeted alpha particle therapy with an actinium-225 labelled antibody for carbonic anhydrase IX. (PubMed, Chem Sci)
    This new H2MacropaSqOEt chelator was used to modify a monoclonal antibody, girentuximab (hG250), that binds to carbonic anhydrase IX, an enzyme that is overexpressed on the surface of cancers such as clear cell renal cell carcinoma...Evaluation of [225Ac]Ac(MacropaSq-hG250) in a mouse xenograft model, that overexpresses carbonic anhydrase IX, demonstrated a highly significant therapeutic response. It is likely that H2MacropaSqOEt could be used to modify other antibodies providing a readily adaptable platform for other actinium-225 based therapeutics.
    Journal
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    CA9 (Carbonic anhydrase 9)
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    CA9 overexpression • CA9 expression
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    Rencarex (girentuximab)
    4ms
    Preclinical Evaluation of virus-like particle Vaccine Against Carbonic Anhydrase IX Efficacy in a Mouse Breast Cancer Model System. (PubMed, Mol Biotechnol)
    This vaccine was tested in a therapeutic setting by using a triple-negative breast cancer mouse model system comprising 4T1, 4T1-Car9 and 4T1-Car9 cells, the latter representing positive and negative controls for murine CAIX production, respectively. The humoural immune responses induced in tumour-bearing animals were predominantly of Th1-type and higher anti-mCAIXc titres correlated with slower growth and lung metastasis development of 4T1 tumours constitutively expressing mCAIX in vivo in the syngeneic host.
    Preclinical • Journal
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    CA9 (Carbonic anhydrase 9)
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    CA9 expression
    5ms
    Ex vivo mass spectrometry-based biodistribution analysis of an antibody-Resiquimod conjugate bearing a protease-cleavable and acid-labile linker. (PubMed, Front Pharmacol)
    In vitro stability analysis showed not only R848 release in the presence of the protease Cathepsin B but also under acidic conditions. The ex vivo mass spectrometry-based biodistribution data confirmed the low stability of the linker-drug connection while highlighting the selective accumulation of the IgG in tumors and its long circulatory half-life.
    Preclinical • Journal
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    CA9 (Carbonic anhydrase 9)
    1year
    Quantitative Imaging of Hypoxic CAIX-Positive Tumor Areas with Low Immune Cell Infiltration in Syngeneic Mouse Tumor Models. (PubMed, Mol Pharm)
    In the future, this technique may enable visualization of CAIX expression before or during hypoxia-targeted or hypoxia-reducing treatments. Thereby, it will help optimize immuno- and radiotherapy efficacy in translationally relevant syngeneic mouse tumor models.
    Preclinical • Journal • Immune cell
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    CA9 (Carbonic anhydrase 9)
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    CA9 expression
    1year
    Data-Driven Identification of Targets for Fluorescence-Guided Surgery in Non-Small Cell Lung Cancer. (PubMed, Mol Imaging Biol)
    EpCAM, CAIX, and Collagen XVII were identified using concomitant use of data-driven selection software and clinical evidence as promising targets for intraoperative fluorescence imaging for both major subtypes of non-small cell lung carcinomas.
    Journal • Surgery
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    FOLR1 ( Folate receptor alpha ) • CEACAM5 (CEA Cell Adhesion Molecule 5) • EPCAM (Epithelial cell adhesion molecule) • CA9 (Carbonic anhydrase 9) • SLC2A1 (Solute Carrier Family 2 Member 1) • TMPRSS4 (Transmembrane Serine Protease 4)
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    CA9 expression • EPCAM expression
    over1year
    The LAG-3/FGL1 Axis is a Dominant Immune Evasion Pathway in NSCLC Modulated by Hypoxia. (IASLC-TTLC 2023)
    Experimental hypoxia is sufficient to alter T-cell function and induce FGL1 expression in tumor cells. Together, our results support the LAG-3/FGL1 axis as a dominant immune evasion pathway in a subset of NSCLCs and modulated by tumor microenvironment hypoxia.
    PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • LAG3 (Lymphocyte Activating 3) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • PD-L2 (Programmed Cell Death 1 Ligand 2) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IL2RA (Interleukin 2 receptor, alpha) • NCAM1 (Neural cell adhesion molecule 1) • TNFRSF9 (TNF Receptor Superfamily Member 9) • CA9 (Carbonic anhydrase 9) • CASP3 (Caspase 3) • CD27 (CD27 Molecule) • LAMP3 (Lysosomal Associated Membrane Protein 3) • VIM (Vimentin) • CD68 (CD68 Molecule) • FOXP3 (Forkhead Box P3) • FGL1 (Fibrinogen Like 1)
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    LAG3 expression • HAVCR2 expression • HIF1A expression • CA9 expression
    over2years
    Novel humanized monoclonal antibodies for targeting hypoxic human tumors via two distinct extracellular domains of carbonic anhydrase IX. (PubMed, Cancer Metab)
    CA9hu-1 and CA9hu-2 are the very first humanized antibodies against CA IX that are likely to become suitable therapies for hypoxic tumors. These antibodies can be applied in the treatment therapy of primary tumors and suppression of metastases formation.
    Journal
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    CA9 (Carbonic anhydrase 9)
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    CA9 expression
    over2years
    Hydrogen-deuterium exchange mass spectrometry reveals three unique binding responses of mAbs directed to the catalytic domain of hCAIX. (PubMed, MAbs)
    Finally, the ability of m4A2 to modulate extracellular pH and intracellular metabolism is reported. By highlighting three unique modes by which hCAIX can be targeted, this study demonstrates both the utility of HDX-MS as an important tool in the characterization of anti-cancer biotherapeutics, and the underlying value of CAIX as a therapeutic target.
    Journal
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    CA9 (Carbonic anhydrase 9)
    over3years
    Immunotherapy with immunocytokines and PD-1 blockade enhances the anticancer activity of Small Molecule-Drug Conjugates targeting Carbonic Anhydrase IX. (PubMed, Mol Cancer Ther)
    Analysis of the microscopic structures of healthy organs performed three months after tumor eradication confirmed absence of pathological abnormalities in the healthy kidney, liver, lung, stomach and intestine. Our findings may be of clinical significance as they provide motivation for the development of combinations based on small molecule-drug conjugates and immunotherapy for the treatment of renal cell carcinoma and of hypoxic tumors.
    Journal
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    CA9 (Carbonic anhydrase 9)
    over3years
    Targeted and redox-responsive drug delivery systems based on carbonic anhydrase IX-decorated mesoporous silica nanoparticles for cancer therapy. (PubMed, Sci Rep)
    In vitro, CAIX capping the doxorubicin hydrochloric (DOX)-loaded nanoparticles (DOX@MSNs-CAIX) exhibited effectively redox-responsive release in the presence of glutathione (GSH) owing to the cleavage of the disulfide bond...Tumor targeting in vivo studies clearly demonstrated DOX@MSNs-CAIX accumulated in tumors and induced more tumor cells apoptosis in 4T1 tumor-bearing mice. With great potential, this drug delivery system is a promising candidate for targeted and redox-responsive cancer therapy.
    Journal
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    CA9 (Carbonic anhydrase 9)
    |
    doxorubicin hydrochloride