CAR-T In Vitro Efficacy Services with OncoSolid™ Liver Cancer Organoid Models

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

Overview

Liver cancer is the second mortality cancer worldwide. The primary liver tumor is of high heterogeneity and often leads to limited responses to clinical treatment among patients. The available tumor cell lines and tissue cultures cannot provide a whole picture of cancer. With extensive discovery experience in tissue culture, Creative Biolabs offers 3D in vitro cancer models that recapitulate key features of liver tumors and microenvironments. The liver cancer organoid is useful in modeling the disease and helping to test the efficacy and safety of drugs and immunotherapies.

Fig.1 Establishing liver cancer organoids for drug screening and efficacy test. (Dong, et al., 2022)

Our Ovarian Cancer Organoids-Based CAR-T Service

Liver Cancer Organoids

Multiple subtypes of liver cancer organoids consist of a high throughput platform for CAR-T efficacy tests.

Fig.2 Subtypes of primary liver cancer. (De Siervi & Turato, 2023)

Primary liver cancer	Proportion
Hepatocellular Carcinoma (HCC)	80%-85%
Cholangiocarcinoma (CCA)	15%-20%

Liver Cancer Organoid Specifications

Type of Organoid	Brief Description	Deliverables	Advantages
PDO/PDXO	Patient-derived organoid Patient-derived xenograft organoid	A dozen of 3D cultures resemble the original diseased liver tissue	Derived from patient disease tissue and resemble primary tissues state
hiPSC-derived Organoid	Human induced pluripotent stem cells derived mesenchymal and endothelial cells co-cultured with Human HCC cells to produce liver organoids.	A dozen of organoids imitate primary liver tissue	Mimic the morphology and function of primary hepatocytes
Adult Stem Cell-derived Organoid	Liver stem cells are cultured in optimized conditions to establish liver organoids.	A dozen of organoid imitate primary liver tissue; tumor-related gene mutated in organoid cultures	Mimic primary hepatocytes activity; long-term maintenance of genomic integrity in cultured cells

Organoids Characterization

We provide a complete evaluation of the normal liver organoids and liver cancer organoids before applying them to CAR-T efficacy tests.

Item	Description
Histological Characteristics	Growth pattern, tissue structure, differentiation grade, and somatic mutations determination
Phenotypic Characteristics	HCC tumor marker-alpha-fetoprotein (AFP), biliary cell markers Keratin 7 (KRT7) and Keratin 19 (KRT19), ductal marker
Related Cell Function and Activities	Albumin secretion, CYP3A activity, LDL uptake and glycogen storage
In Vivo Verification	Transplantation to mouse to evaluate tumor formation in vivo

Our Liver Cancer-related CAR-T Products and Services

We provide liver-targeted CAR-T products and one-stop CAR-T therapy development services for in vitro anti-tumor efficacy evaluation. Products include CAR vector products, CAR cells, viral particle products, but not limited to this.

Target Antigen	Target Description	CAR-T product
EGFR	Epidermal growth factor (EGF)-EGF receptor signaling pathway involves in hepatocellular carcinoma development, including cancer proliferation, and metastasis and can be potential target for therapeutics.	Anti-EGFR CAR-T
EpCAM	Epithelial cell adhesion molecule (EpCAM) is identified as a marker for liver cancer stem cells and is overexpressed in hepatocyte epithelial tissues.	Anti-EpCAM CAR-T
AFP	AFP (alpha-fetoprotein) is a liver cancer marker presented on the tumor cells surface in complex with MHC I molecular.	Anti-AFP CAR-T
c-MET	c-Met is the human hepatocyte growth factor (HGF) receptor and is overexpressed in hepatocellular carcinoma and has low expression in normal tissues.	Anti-c-MET CAR-T
DR5	DR5 is death receptor 5 and is one of the tumor necrosis factor-receptor of the TNFRSF superfamily. Soluble DR5 is accurately related to the prognosis of HBV-HCC patients.	Anti-DR5 CAR-T
Glypican3	Glypican3(GPC3) is a cell surface proteoglycan that overexpressed in hepatocellular carcinoma tissues but rarely expressed in healthy adult liver.	Anti-Glypican3 CAR-T

Published Data

Patient-derived Cholangiocarcinoma (CCA) Organoid Model
Patient-derived cholangiocarcinoma (CCA) organoid model is derived from fragments of the surgical specimen and showed an organoid phenotype 2 days after seeding. The organoid of CCA has similar cellular components to its source tumor, identified are staining with epithelial cells, bile duct, mucin, and stem cell markers.
Fig.3 Cystic organoids are established from human intrahepatic CCA (iCCA) and mimic the features of the primary tumor. (Li, et al., 2019)

Online Inquiry

Creative Biolabs is committed to offering advanced organoids technology for cancer research and investigation of tumor responses to CAR-T therapies. Please contact us and find out how we can help you.

References

Li, L.; et al. Human primary liver cancer organoids reveal intratumor and interpatient drug response heterogeneity. JCI insight. 2019, 4(2): e121490.
Dong, R.; et al. Liver organoids: an in vitro 3D model for liver cancer study. Cell Biosci. 2022, 12: 152.
De Siervi, S., & Turato, C. Liver Organoids as an In Vitro Model to Study Primary Liver Cancer. International journal of molecular sciences. 2023, 24(5): 4529.