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

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

Bladder Cancer Organoid (BCO) Models

Cancer organoid is a prevailing in vitro model to study the mechanism of tumorigenesis and serves as a clinically related, easy-to-use tool to test the sensitivity of drugs and immunotherapeutics for cancer treatment. Creative Biolabs has developed a cancer organoid platform, including various cancers, to evaluate CAR‐T cells mediated killing against solid tumors. The patient-derived bladder cancer organoids resemble the heterogeneity and biological characteristics of tumor tissue of origin and can be used to predict CAR-T therapeutic responses in vivo.

Fig.1 Establishing well-characterized bladder cancer organoids for potent therapy development. (Lee, et al., 2018)

Bladder Cancer Organoid Subtypes

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

Types of bladder cancer and derived organoids

Type	Organoids Subtypes	Organoid Identification
Invasive bladder cancer (MIBC)	Luminal	Luminal markers CK20 Uroplakin II GATA3	Epithelial marker E‐cadherin Proliferation marker Ki67
Non‐muscle‐invasive bladder cancer (NMIBC)	Basal	Basal markers CK5 P63 CD44	Epithelial marker E‐cadherin Proliferation marker Ki67

Culture Medium

Classic medium complement with growth factor, R‐spondin 1 and noggin, can support patient-derived bladder cancer cultivation.
Other formulas with different molecules and growth factors can be explored for customized needs.

Tumor Marker Identification in Organoids

All bladder cancer-related protein antigens are tested to determine the antigen profile of established organoids using specific antibodies.

Techniques
Immunohistochemistry				Fluorescence Microscopy
Potential Targets
B7‐H3	vEGFR2	CEACAM5	HER2	FRα	GD2
PSCA	MSLN	PD‐L1	CD44v6	PSMA	EGFRvIII

Our Bladder Cancer Organoids-based CAR-T Efficacy Test Service

Bladder cancer organoids and CAR-T cells cooperate in the co-culture system to test the response of BCOs to immunotherapies in vitro. Specific killing of CAR-T is assessed using cytotoxic assays and ELISA test of cytokine secretion.

Fig.2 Workflow of the co-culture system for CAR-T efficacy tests. (Creative Biolabs)

Bladder Cancer-related CAR-T Products and Services at Creative Biolabs

Creative Biolabs possess a wide range of CAR-T products and kits for bladder cancer study, including CAR vectors, viral particle packaging kits, CAR cells, and so on. Our products have been validated with high performance by global clients.

Target Antigen	Target Description	CAR-T Products
MUC1	The expression of MUC1 is elevated in urothelial carcinoma, especially in metastatic carcinoma.	Anti-MUC1 CAR-T
c-FOS	Carcinogenesis of bladder cancer can be suppressed by targeting c-FOS.	Anti-c-FOS CAR-T
PSCA	Prostate stem cell antigen (PSCA) is a cell surface protein and has an overexpression on various tumors, such as bladder, prostate, gastric cancers, and pancreatic cancers.	Anti-PSCA CAR-T

Case Study

Utilizing Bladder Cancer Organoids as a Model to Evaluate CAR-T Cell Function
Organoids	Source: cystectomy specimens from patient Organoid name: invasive bladder cancer organoids Identified target antigen: MUC1
CAR-T cells	Cell name: second generation MUC1 CAR‐T cells Control cells: CD19 CAR‐T cells
Results of efficacy test	MUC1+ organoids are deformed and lysed after co-culturing with MUC1-targeted CAR-T cells. Directional moving of anti-MUC1 CAR-T cells towards MUC1+ cancer organoids. LDH release and cytokines secretion is significantly increased from MUC1+ organoids when incubated with anti-MUC1 CAR-T cells.
Fig.3 Specific cytotoxicity of CAR-T cell in bladder cancer organoids. (Yu, et al., 2021)

Creative Biolabs has extensive experience in organoids and CAR-T research. If you are interested in our products or services, please do not hesitate to contact us.

References

Yu, L.; et al. Patient-derived organoids of bladder cancer recapitulate antigen expression profiles and serve as a personal evaluation model for CAR-T cells in vitro. Clinical & translational immunology. 2021, 10(2): e1248.
Lee, S. H.; et al. Tumor Evolution and Drug Response in Patient-Derived Organoid Models of Bladder Cancer.Cell. 2018, 173(2): 515–528.e17.