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

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

Brain Cancer Organoid Models Fig.1 Immunofluorescence image of brain organoids.
(Nowogrodzki, 2018)

Brain Cancer Organoid Models

3D in vitro organoid models have become the most popular tool in brain and related disease research. Glioblastoma is the most reported brain cancer with a poor prognosis and survival rate. Organoids recapitulate the genotype and phenotype of primary tumors of cancer and may be a suitable model to imitate the inter- and intra-tumoral heterogeneity in vivo.

With extensive experience in stem cell research, Creative Biolabs is competent in tissue processing, stem cell culture, and differentiation. We offer a brain cancer organoid platform for investigating CAR-T response in patients by applying powerful immunohistology, fluorescence microscopy, and advanced image capture and analysis techniques.

Fig.2 Establish brain cancer organoids from PSC using Nucleofection. (Ogawa, et al., 2018)

Key Features of The Brain Cancer Organoid Model

Recapitulate the cellular heterogeneity and molecular features of initial tumor tissue.
Hypoxia gradients present in cancer organoid is detected in GBOs by a probe.
Active cell proliferation is observed at the border of organoids and reversely in the core.

Workflow

Different Pathways for Brain Cancer Organoid Generation

Patient-derived Organoid Models

Cancer stem cell grows and differentiates into various brain associated cells and recapitulate the hypoxic state of tumor.
Matrigel-based culture; Matrigel-free culture method.

Genetically Engineered Brain Organoids

Brain organoids established from hPSCs are edited to develop tumor.
Induce tumorigenesis in brain organoid using genome editing technique by overexpression of oncogenes and/or disturb tumor suppressor gene functions.

Cancer Cells Integrated Brain Organoids

Patient-derived glioblastoma stem cells (GSCs) co-culture with normal brain organoids to induce tumor.
Cancer cells integrate into normal organoids and retain genetic background of the primary tumor.

Characterization of the Established Organoids

The histological and genomic characteristics of the established organoids and the initial tumors are measured, using various advanced tumor profiling technologies.

Phenotypic Characterization

H&E staining
Alcian blue staining
IHC (Immunohistochemistry)

Molecular Characterization

DNA sequencing
RNA sequencing
Epigenomics

Highlights

01Establishing organoids with stable efficiency, routinely 2-4 weeks.

02CAR-T efficacy test is completed in one week.

03Organoids allow genome edition using transposon, CRISPR-Cas9, and lentivirus.

04The success rate for GBOs ranges from 75% to 95%.

Our Brain Cancer-related CAR-T Products for Anti-tumor Efficacy Evaluation

Creative Biolabs provides a full range of key products associated with CAR-T cell development. The list presents brain cancer-related antigen proteins and related products and can be applied to in vitro and in vivo validation assays.

Target antigen	Target description	CAR-T cell
GD2	GD2, also called ganglioside G2 or GRD2, is over-expressed on neuroectoderm-initiated tumor cells.	Anti-GD2 CAR-T
VEGFR2	VEGFR2 is one of the receptors of vascular endothelial growth factor (VEGF), and the interaction of the two proteins mediates endothelial growth and movement.	Anti-VEGFR2 CAR-T
EGFRvIII	EGFRvIII is a variant of EGFR (Epidermal growth factor receptor) with the deletion of six exons in the EGFR gene and is of high expression in glioblastoma.	Anti-EGFRvIII CAR-T

Case Study

Establishing A Living Biobank of Patient-derived Glioblastoma Organoids and Its Use for CAR-T Efficacy Tests
Highlights: Glioblastoma organoids (GBOs) are generated from clinical tumor tissue samples. Organoids are cultured in a component-defined medium and retain the diversity of tissue cells. Tumor marker of EGFRvIII is maintained in the organoids, and anti-EGFRvIII CAR-T cells showed specific killing on EGFRvIII+ GBOs.
Fig.3 Increased cytokines (IL-2, TNF-α, and IFN-γ) production after co-culture of EGFRvIII+ organoids with targeted CAR-T cells. (Jacob, et al., 2020)
Fig.4 Combined immunohistochemical staining and confocal image to analyze CAR-T cell proliferation, tumor organoids apoptosis and antigen loss after incubation with specific CAR-T. (Jacob, et al., 2020)

Creative Biolabs offers advanced organoid technologies and high-quality cancer organoids for cancer biology discovery. The organoid model system is also a functional platform for drug efficacy tests. If you are interested in our services, please contact us for a quote.

References

Nowogrodzki, Anna. How cerebral organoids are guiding brain-cancer research and therapies. Nature. 2018, 561(7724): S48-S49.
Ogawa, J.; et al. Glioblastoma Model Using Human Cerebral Organoids. Cell reports. 2018, 23(4): 1220-1229.
Jacob, F.; et al. Generation and biobanking of patient-derived glioblastoma organoids and their application in CAR-T cell testing. Nature protocols. 2020, 15(12): 4000-4033.