codrituzumab (RG7686) / Roche - LARVOL DELTA

Glypican-3-Targeted Paired Radiotheranostics in Orthotopic Liver Cancer Models. (PubMed, Clin Cancer Res) - "We show GPC3-specific PET imaging can predict and assess response to GPC3-targeted alpha particle therapy in orthotopic liver cancer models. This approach can address the unmet diagnostic and therapeutic needs for patients with liver cancer and may extend to other GPC3-expressing malignancies."

Journal • Preclinical • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • GPC3

Metagenomic analysis of water column samples collected from Green Canyon 233 prior to the Deepwater Horizon incident. (PubMed, Appl Environ Microbiol) - "Here, we analyze metagenomic sequencing of 10 water column samples collected from the Green Canyon 233 (GC233) lease block near the mussel-fringed brine lake, Brine Pool NR-1...Our metagenomic libraries, although not derived from the same lease block as the blowout, contribute linkages between microbial taxonomy and function in an area of active oil and gas production. This analysis can aid microbial indicator development, machine learning, and modeling efforts to bioremediate hydrocarbon influxes in marine environments."

Journal

Genomic characterization of a pathogenic Bacillus licheniformis strain LSDY01: deciphering its genetic diversity and virulence-associated traits. (PubMed, Front Microbiol) - "A unique horizontally acquired genomic island (~157 27 kb, GC 33.03%) and a putative type IV secretion system (T4SS) gene cluster were identified on the chromosome of this strain...LSDY01 was susceptible to imipenem and vancomycin but resistant to penicillin, erythromycin, and chloramphenicol. The CCK-8 assay revealed a non-significant trend toward reduced HEK293 cell viability after co-culture with LSDY01 (p = 0.0545 at 2 h of CCK-8 incubation). Our findings suggest that horizontal gene transfer, including plasmid acquisition and potential phage integration, may have enabled B. licheniformis to evolve into a pathogen, highlighting the need to reassess the safety of traditionally non-pathogenic microbes."

Journal • Dermatology • Gene Therapies • Infectious Disease

Enhanced solid tumor rejection using IF-BETTER gated CAR T cells for the treatment of hepatocellular carcinoma (AACR 2026) - "We identified IL1RAP as a potential CCR target and paired the GPC3 CAR, incorporating the GC33 scFv and the 1XX signaling module to extend CAR T cell persistence, with CCRs providing different costimulatory signals...In summary, combining calibrated 1XX CAR signaling with IL1RAP‑gated costimulation increases GPC3 CAR T cell persistence and reduces antigen escape. These data support the clinical translation of an IF-BETTER gated strategy targeting GPC3 in hepatocellular carcinoma."

CAR T-Cell Therapy • Hematological Malignancies • Hepatocellular Cancer • Oncology • Solid Tumor • IL1RAP

Iterative engineering of GPC-3 targeted synthetic TCR and antigen receptor (STAR) cells in advanced solid tumors (AACR 2026) - P1 | "We further optimized the construct to enhance T-cell expansion and persistence, leading to a v3 version armored with membrane-bound IL-15 (mbIL-15). The STAR-T platform utilizes a high-affinity GPC3-specific scFv (GC33) fused to TCR constant domains... Iterative engineering of GPC3-targeted STAR-T cells with functionalities to enhance tumor trafficking (CXCR2) and persistence (mbIL-15) results in potent anti-tumor activity. Early clinical data demonstrate a favorable safety profile and promising efficacy in heavily pretreated patients with GPC3-positive solid tumors. These findings validate our optimization strategy and support the continued clinical development of YTS102 as a promising therapeutic for solid tumors."

First-in-human • Metastases • Gastric Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CXCR2 • GPC3 • IL15

Chimeric Antigen Receptor-Glypican-3 T Cell Therapy CAR001 for Advanced Hepatocellular Carcinoma: a first-in-human, phase I Trial (IMMUNOLOGY 2026) - "A clinical trial in 10 GPC3⁺ patients was conducted via HAI or IV, with doses from 9E7 to 6E8 CAR-T cells. We identified high cell-surface-GPC3 binding sequence (EC₅₀ ratio vs GC33 = 0.023:0.203). CAR001 represents a promising advance in the treatment of advanced HCC with manageable safety. Patients with greater expansion tended to have deeper drops in DCP but not observed for AFP. Higher DP IFNg secretion inversely correlated with AFP reduction and DCP reduction."

First-in-human • Metastases • P1 data • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3 • IFNG

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

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

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 2026 ➔ Jun 2027 | Trial primary completion date: Jun 2026 ➔ Jun 2027

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

Glypican-3: Novel Theranostic Agent for Hepatocellular Carcinoma. (PubMed, Semin Nucl Med) - "First-in-human studies, including 124I-codrituzumab and 68Ga-RAYZ-8009, confirmed tumor-specific accumulation but remained limited in scale...The available evidence suggests a preferential pathway, involving the selection of a limited set of lead vectors, their pairing with suitable radionuclides, validation in orthotopic/PDX models using standardized endpoints, and the integration of comprehensive dosimetric and toxicologic studies before proceeding to broader human trials. GPC3-directed theranostics thus offers a compelling, disease-specific route to precision management of HCC, provided translational rigor addresses the outlined safety and quantitative imaging gaps."

Journal • Review • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

Comparative effectiveness and safety of second-line therapies and dosing regimens for advanced hepatocellular carcinoma: a network meta-analysis. (PubMed, Eur J Gastroenterol Hepatol) - "Brivanib 800 mg once daily (OD) was most effective in terms of ORR [odds ratio (OR) = 7.13, 95% CI = 1.42, 35.88], while apatinib 750 mg QD ranked highest for DCR (OR = 3.92, 95% CI = 1.76, 8.71). Codrituzumab 1600 mg administered every 2 weeks demonstrated the most advantageous health profile, markedly decreasing AEs and instances of grade 3-4 AEs...Cabozantinib 60 mg QD and pembrolizumab 200 mg Q3W arise as the most suitable second-line therapies alternatives for advanced HCC, offering substantial improvements in survival and disease control with manageable adverse effects. These findings support the integration of both targeted and immune therapies in handling of advanced HCC."

HEOR • Journal • Retrospective data • Hepatocellular Cancer • Oncology • Solid Tumor

Therapeutic Glypican-3 CRISPR Genome-Editing Using UltraLarge Porous Silica Nano-Depot for the Treatment of Hepatocellular Carcinoma. (PubMed, Small Sci) - "Furthermore, the GPC3 CRISPR-Cas9@UPSND treatment exhibits superior anti-proliferative efficacy in tumor-growth prevention compared to Codrituzumab, as evidenced by the analysis of Ki67 and GPC3 expression, along with serum GPC3 levels. These findings underscore the translational potential of the non-viral UPSND nanoplatform-based CRISPR GPC3 genome editing, offering a promising targeted therapeutic strategy for HCC treatment."

Journal • Gene Therapies • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • GPC3

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

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

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