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DRUG:

codrituzumab (RG7686)

i
Other names: RG7686, GC33, GC-33, RG-7686, RO 5137382, RO-5137382, RO5137382, GC 33, RG 7686
Company:
Roche
Drug class:
GPC-3 inhibitor
3ms
Glypican-3 deficiency in liver cancer upregulates MAPK/ERK pathway but decreases cell proliferation. (PubMed, Am J Cancer Res)
To confirm the usefulness of the models for GPC3-targeted drug development, we evaluated the target engagement of a GPC3-selective antibody, GC33, conjugated to the positron-emitting zirconium-89 (89Zr) in subcutaneous murine xenografts of wild type (WT) and KO liver cancer cell lines...KO lines demonstrated increased sensitivity to ERK (GDC09994), while AKT (MK2206) inhibition was more effective in WT lines...We show that GPC3-KO liver cancer cell lines exhibit decreased tumorigenicity and altered signaling pathways, including upregulated pMAPK/ERK1/2, compared to parental lines. Furthermore, we successfully distinguished between GPC3+ and GPC3- tumors using the GPC3-targeted immunoPET imaging agent, demonstrating the potential utility of these cell lines in facilitating GPC3-selective drug development.
Journal
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GPC3 (Glypican 3)
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MK-2206 • codrituzumab (RG7686)
4ms
Preparation of bacterial outer membrane vesicles with anti-GPC3 single-chain antibody and identification of their targeting effects on hepatocellular carcinoma (PubMed, Sheng Wu Gong Cheng Xue Bao)
The Hbp-hGC 33-OMVs prepared in this study demonstrated stronger ability of binding to Hep G2 cells than the wild-type OMVs (P=0.008). All the data indicated that Hbp-hGC 33-OMVs with anti-GPC3 single-chain antibody were successfully prepared and could be used for research on the targeted therapy of hepatocellular carcinoma.
Journal
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GPC3 (Glypican 3)
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codrituzumab (RG7686)
5ms
Development of GPC3-CAR-NK cells and optimization as a therapy for HCC. (PubMed, J Leukoc Biol)
Finally, the combination of microwave ablation with GC33-G2D-NK cell administration showed greater CAR-NK infiltration and tumor regression in ablated tumors than monotherapy alone. These findings indicate that administration of GPC3-CAR-NK cells may be a potential strategy for the treatment of HCC, and regional delivery or their combination with microwave ablation may optimize their efficacy against HCC and may have translational value.
Journal
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GPC3 (Glypican 3)
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codrituzumab (RG7686)
8ms
Artificial intelligence (AI)-powered quantification of glypican-3 (GPC3) expression facilitates patient selection for GPC3-targeted therapy in solid tumors (AACR 2024)
FFPE slides were stained for GPC3+ (GC33, Ventana), PD-L1+ (22C3, Dako) cells and then scanned at 20x using the Aperio Versa8 scanner... Here we profiled GPC3 expression across tumor types and showed high level of expression in HCC followed by SQ-NSCLC. We have established an AI-powered digital pathology platform that can provide a standardized, scalable, and reproducible method of characterizing GPC3 positivity to support further patient selection in clinical study.
Clinical • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • GPC3 (Glypican 3)
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PD-L1 expression • GPC3 expression
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PD-L1 IHC 22C3 pharmDx
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codrituzumab (RG7686)
12ms
Genetically engineered nano-melittin vesicles for multimodal synergetic cancer therapy. (PubMed, Bioeng Transl Med)
VAM generated from the cellular plasma membrane was bio-synthetically fabricated, with the recombinant protein (hGC33 scFv-melittin) being harbored and displayed on the cell membrane...Nanomelittin formed pores in membranes and disturbed phospholipid bilayers, which allowed the anticancer agents (i.e., chemotherapeutic drug doxorubicin and sonosensitizer purpurin 18 nanoparticles) co-delivered by VAM to penetrate deeper tumor sites, leading to synergistic therapeutic effects. In particular, the punching effect generated by sonodynamic therapy further improved the immunomodulatory effect of nanomelittin to activate the immune response. Taken together, our findings indicate that clinically translatable VAM-based strategies represent a universal, promising approach to multimodal synergetic cancer therapy.
Journal
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MMP14 (Matrix Metallopeptidase 14)
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doxorubicin hydrochloride • codrituzumab (RG7686)
1year
A novel bispecific antibody as an immunotherapeutic agent in hepatocellular carcinoma. (PubMed, Mol Immunol)
GC33, a humanized mAb directed against GPC3, is a safe and well-tolerated therapy choice for patients with HCC, which tested in a phase I trial in advanced HCC patients...CD16A activation and increased cytokines release were associated with higher anti-tumor activity. In conclusion, this bispecific antibody may possibly help develop new therapeutic strategies for HCC and develop new treatment options in the future.
Journal • IO biomarker
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GPC3 (Glypican 3) • FCGR3A (Fc Fragment Of IgG Receptor IIIa)
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GPC3 expression
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codrituzumab (RG7686)
over1year
A Study of Codrituzumab in Children and Young Adults With Solid Tumors and Have Not Responded to Treatment or Have Come Back After Treatment (clinicaltrials.gov)
P1, N=50, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025
Trial completion date • Trial primary completion date
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GPC3 (Glypican 3)
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GPC3 expression
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codrituzumab (RG7686)
over2years
Glypican-3 (GPC3) is associated with MCPyV-negative status and impaired outcome in Merkel cell carcinoma. (PubMed, Oncotarget)
GPC3 expression is frequent in MCC tumors, especially MCPyV-negative cases, and is associated with increased risk of death. High prevalence of surface GPC3 makes it a putative drug target.
Journal • IO biomarker
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GPC3 (Glypican 3)
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GPC3 expression
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codrituzumab (RG7686)
over2years
HBZmacropa-NCS: A Bifunctional Chelator for Actinium-225 Targeted Alpha Therapy. (PubMed, Bioconjug Chem)
Although both conjugates were comparably effective in their radiolabeling efficiencies, [Ac]Ac-GC33-BZmacropa showed slightly poorer serum stability and biodistribution than [Ac]Ac-GC33-macropa. Together, these results establish HBZmacropa-NCS as a new bifunctional chelator for the preparation of Ac radiopharmaceuticals.
Journal
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GPC3 (Glypican 3)
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codrituzumab (RG7686)
over2years
Glypican-3 immunohistochemistry precision, validation, and prevalence in selected solid tumors to identify target populations for CAR T cell therapy (AACR 2022)
GPC3 has a high prevalence in selected tumors with low level expression in some normal tissues, making it an attractive target for CAR T cell therapy. The GC33 clone performs similarly to 1G12 and could be used for IHC screening for CAR T cell therapy. MRCLS has higher prevalence of GPC3+ expression relative to other LS subtypes.
Clinical • CAR T-Cell Therapy
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GPC3 (Glypican 3)
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GPC3 expression
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codrituzumab (RG7686)
almost3years
Novel low-avidity glypican-3 specific CARTs resist exhaustion and mediate durable antitumor effects against hepatocellular carcinoma. (PubMed, Hepatology)
The novel low-avidity 8F8-BBz CART resists exhaustion and apoptosis inside tumor lesions, demonstrating a greater therapeutic potential than high-avidity CARTs.
Journal
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GPC3 (Glypican 3)
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codrituzumab (RG7686)
over3years
New P1 trial
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GPC3 (Glypican 3)
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GPC3 expression
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codrituzumab (RG7686)
over3years
Recombinant immunotoxin targeting GPC3 is cytotoxic to H446 small cell lung cancer cells. (PubMed, Oncol Lett)
An immunotoxin carrying an anti-GPC3 antibody (hGC33) and Pseudomonas aeruginosa exotoxin A 38 (PE38) was generated...Cell surface-bound GPC3 was abundant on the membranes of H446 cells, but absent on H510A. Altogether, the present findings suggested that GPC3 could be considered as a potential therapeutic target for SCLC immunotherapy.
Journal • IO biomarker
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GPC3 (Glypican 3)
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codrituzumab (RG7686)
almost4years
Glypican-3-Targeted Alpha Particle Therapy for Hepatocellular Carcinoma. (PubMed, Molecules)
GC33 is a full-length humanized monoclonal IgG1 specific to GPC3 that can localize to HCC in vivo...Our studies highlight a significant disadvantage of using directly-labeled biomolecules with long blood circulation times for TAT. Strategies to mitigate such treatment toxicity include dose fractionation, pretargeting, and using smaller targeting ligands.
Journal
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GPC3 (Glypican 3)
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codrituzumab (RG7686)
almost4years
hGC33-Modified and Sorafenib-Loaded Nanoparticles have a Synergistic Anti-Hepatoma Effect by Inhibiting Wnt Signaling Pathway. (PubMed, Nanoscale Res Lett)
We conclude that hGC33 increases the targeting of SFB-NP to HCC cells. hGC33-SFB-NP synergistically inhibits the progression of HCC by blocking the Wnt pathway and the Ras/Raf/MAPK pathway.
Journal
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CCND1 (Cyclin D1) • GPC3 (Glypican 3)
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CCND1 expression
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sorafenib • codrituzumab (RG7686)