codrituzumab (RG7686) / Roche - LARVOL DELTA

Engineered E. coli OMVs Carrying the Membrane-Binding hGC33 Fragment Precisely Target Liver Cancer and Effectively Treat Tumor. (PubMed, Int J Nanomedicine) - "Meanwhile, hGC33-OMVs suppressed HepG2 cell proliferation, induced G1-phase arrest, and reduced Wnt3a, β-catenin, Cyclin D1, and C-myc expression. Engineered E. coli hGC33-OMVs effectively target HCC via the hGC33-GPC3 interaction, inhibit tumor growth by suppressing Wnt signaling, and demonstrate potential for use as a versatile platform for antibody delivery."

Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • CCND1 • CTNNB1 • GPC3 • MYC • PCNA • WNT3A

Hepatocellular Carcinoma and Antibody Drug Conjugates: A Systematic Review. (PubMed, Cureus) - "Recent clinical trials have demonstrated that ADCs targeting GPC3, such as GC33 and 32A9, show promising results in reducing tumor growth and improving patient outcomes in advanced HCC...The exclusion criteria included languages other than English and publications before 2019. A total of 26 articles were identified, and 12 articles were selected after quality assessment."

Journal • Review • Fibrosis • Gastroenterology • Genetic Disorders • Hepatitis B • Hepatitis C • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Liver Cancer • Liver Cirrhosis • Metabolic Disorders • Oncology • Solid Tumor • GPC3

CRISPR-mediated glypican-3 genome editing via ultra-large porous silica nanoparticles in hepatocellular carcinoma therapy (AACR 2025) - "ULSN presents strong potential as a non-viral delivery system for CRISPR-Cas9 RNP targeting GPC3 in HCC, offering improved gene delivery efficiency over lipid-based nanomaterials. This approach not only enhances tumor growth suppression, but also promotes T cell infiltration, ensuring effective and lasting therapeutic outcomes through GPC3 deletion."

Hepatocellular Cancer • Oncology • Solid Tumor • CD4 • CD8 • GPC3

The complete chloroplast genome and phylogenetic analysis of Cinnamomum daphnoides (Laurales: Lauraceae). (PubMed, Mitochondrial DNA B Resour) - "This study presents the complete chloroplast genome of Cinnamomum daphnoides (154,121 bp, GC 39.2%), a newly recorded species in China, revealing a typical quadripartite structure: a large single-copy region (93,688 bp, GC 37.9%), a small single-copy region (18,929 bp, GC 33.9%), and two inverted repeats (20,752 bp each, GC 44.3%)...Phylogenetic analysis groups C. daphnoides with C. tamala, differing from prior studies. These findings clarify its systematic position within Cinnamomum and support its potential for coastal greening applications."

Journal

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 | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Oncology • Pediatrics • Solid Tumor • GPC3

Glypican-3 is a key tuner of the Hedgehog pathway in COPD. (PubMed, Heliyon) - "GPC3 pharmacological modulation was achieved with Codrituzumab during AEC differentiation...GPC3 appears as a crucial co-receptor for the HH pathway in the respiratory context. The modulation of GPC3 may represent a novel experimental strategy to tune HH signalling in therapeutic perspectives."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • GLI2 • GPC3

Idarubicin-loaded chitosan nanobubbles to improve survival and decrease drug side effects in hepatocellular carcinoma. (PubMed, Nanomedicine (Lond)) - "To enhance their action, a targeting agent, such as the humanized anti-GPC3 antibody GC33 (condrituzumab), could be attached to their surface. In HUH7 tumor-bearing xenograft mice, CS-NBs loaded with idarubicin and conjugated or not conjugated with 4A1 were both able to slow tumor growth, to increase mouse survival time compared to free idarubicin (p = 0.00044 and 0.0018, respectively) as well as to reduce drug side effects. CS-NBs loaded with idarubicin can be a useful drug delivery strategy for HCC treatment."

Adverse events • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

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 • Gastrointestinal Cancer • Hepatoblastoma • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • GPC3

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 • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

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 • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

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 • IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • GPC3 • PD-L1

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 • Hematological Disorders • Oncology • MMP14

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."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • FCGR3A • GPC3

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 | Sponsor: 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 • Gastrointestinal Cancer • Oncology • Pediatrics • Solid Tumor • GPC3

The Effects Of Equine-assisted Therapy On Gait In Adults With Parkinson's Disease: A Preliminary Analysis (ACSM 2023) - "There is an observable trend towards significance in each gait variable immediately after 8 weeks of EAT. The study is ongoing and will further explore these differences.VariablePre-EATMidwayIP-EATP8-EATP16-EATGait velocity (cm/s)*101.8±29.1109.2±34.9116.3±32.8105.7±26.2108.0±25.4Step length (cm)116.7±24.6118.8±24.8126.0±27.4118.4±20.2122.5±19.7Time in stance (%GC)66.4±3.366.5±3.365.0±2.765.8±2.866.2±3.1Time in swing (%GC)33.6±3.333.5±3.335.0±2.734.2±2.833.8±3.1Toe clearance (cm)8.7±2.28.7±2.69.5±2.58.9±1.68.7±1.8Values are mean ± s.d. * = main effect for time point (p=0.03); EAT = equine-assisted therapy; Pre-EAT = measurements before EAT; IP-EAT = measurements immediately post EAT; P8-EAT = measurements 8 weeks post-EAT; P16-EAT = measurements 16 weeks post-EAT."

Clinical • CNS Disorders • Movement Disorders • Parkinson's Disease

Expansion of CD33-Edited CD34+ Cells by Gemtuzumab Ozogamicin for In Vivo HSC Gene Therapy of Hemoglobinopathies (ASGCT 2023) - "Here we developed a multiplex adenine base editing approach, by using a HDAd5/35++ vector to simultaneously: i) mutate the splice acceptor site to eliminate the second exon of CD33 (which encodes for the GO target epitope) and ii) inactivate a BCL11a repressor site within the HBG1/2 promoters to reactivate γ-globin (HDAd-ABE8e-sgHBG-sgCD33). Optimization of the editing efficacy and GO concentrations for selection of double edited CD34+ cells in vitro (with additional CD34+ cell donors) and in vivo, in humanized mice, are ongoing. Overall, these data indicate that CD33-based selection of edited HSPCs could improve our in vivo HSC gene therapy approach."

Gene therapy • IO biomarker • Preclinical • Gene Therapies • Hematological Disorders • Sickle Cell Disease • CD33 • CD34 • CD38 • THY1

Genome-wide identification and expression analysis of BrAGC genes in Brassica rapa reveal their potential roles in sexual reproduction and abiotic stress tolerance. (PubMed, Front Genet) - "Collectively, we identified that BrAGC26, BrAGC33, and BrAGC44 have the greatest potential in regulating pollen-pistil interaction and abiotic stress tolerance, respectively. Our findings will aid future functional investigations of BrAGCs in B. rapa."

Journal

Novel intermediate-avidity glypican-3 specific CARTs resist exhaustion and mediate durable antitumor effects against human hepatocellular carcinoma (SITC 2022) - "Remarkably, the tumor infiltrating 8F8 CARTs were much less exhausted and apoptotic, and more functional than GC33 CARTs. Conclusions The novel intermediate-avidity 8F8-BBz CART resists exhaustion and apoptosis inside solid tumors, demonstrating a greater and durable therapeutic potential than high-avidity CARTs."

Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

Ru-based Metal-Organic Nanoradiosensitizers Enhance Radiotherapy by Combining ROS Generation and CO Gas Release. (PubMed, Angew Chem Int Ed Engl) - "Meanwhile, the full-length antiglypican 3 (GPC3) antibody (hGC33) expressed cell membrane coating enabled actively tumor sites targeting with optimized biocompatibility. These results indicate that the ZrRuMn-MONs@mem represent a starting point for advancing an all-around radiosensitizer to potentiate clinical XDT efficiency."

Journal • Oncology • GPC3

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."

IO biomarker • Journal • Genetic Disorders • Immune Modulation • Inflammation • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • GPC3

Nanoparticles Loaded with GSK1059615 Combined with Sorafenib Inhibited Programmed Cell Death 1 Ligand 1 Expression by Negatively Regulating the PI3K/Akt/NF-κB Pathway, Thereby Reversing the Drug Resistance of Hepatocellular Carcinoma to Sorafenib. (PubMed, J Biomed Nanotechnol) - "PLGA-PEG-mal diblock copolymer was used to load GSK1059615 and sorafenib, and the vector was further modified with GPC3 antibody (hGC33) to obtain hGC33-modified GSK1059615 and sorafenib-loaded nanoparticles (Ab-G/S-NP). Ab-G/S-NP regulated the activation of cellular signaling pathways in HCC cells by inhibiting the expression and activation of NF-κB and downregulating the level of programmed cell death 1 ligand 1(PD-L1) to reverse drug resistance of HCC cells to sorafenib. These findings deserve further study in the combined treatment of HCC cells with GSK1059615 in vivo to develop a more effective treatment of sorafenib-resistant cancers."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3 • PD-1 • PD-L1

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 • Gastrointestinal Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • GPC3

Novel low-avidity glypican-3 specific CARTs resist exhaustion and mediate durable antitumor effects against hepatocellular carcinoma (IMMUNOLOGY 2022) - "The novel low-avidity 8F8-BBz CART resists exhaustion and apoptosis inside tumor lesions, demonstrating a greater therapeutic potential than high-avidity CARTs."

Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

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."

CAR T-Cell Therapy • Clinical • Liposarcoma • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Ovarian Serous Adenocarcinoma • Sarcoma • Solid Tumor • GPC3

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 • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3