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

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

Sarcoma Cancer Organoid Models

Sarcomas are derived from mesenchymal cells and are of high malignancy. Many gene mutations in mesenchymal cells result in more than 200 histological subtypes of Sarcoma in this cancer group. Because of its low incidence rate, there is limited biological material and preclinical models for fundamental and preclinical studies. With the development of stem cell methodology, 3D organoid models are generated to represent specific solid tumors in patients and recapitulate native histopathological and genetic features of tumor tissue.

Creative Biolabs offers a valuable system of cancer organoid cultures retaining the biological characteristics of native tumors for large-scale CAR-cell function evaluation in vitro.

Sarcoma organoids integrated with the immune system are used for immunotherapy assessment. Fig.1 Sarcoma organoids integrated with the immune system are used for immunotherapy assessment. (Forsythe, et al., 2022)

Workflow

Workflow

Key Features of the Organoid Models

  • Recapitulate the cellular heterogeneity and molecular features of initial tumor tissue
  • Establishing organoids with stable efficiency, routinely 2-4 weeks
  • Sarcoma organoids integrated with immune system
  • Advanced organoid imaging and immunostaining techniques

Culture System

Culture Medium

The optimal culture medium contains basal medium supplemented with crucial and necessary growth factors and signal molecules to maintain cell culture.

Cell Scaffold

We provide various extracellular matrix (ECM) substitutes as a choice, including Basement membrane matrix, collagen-gel, hydrogel, and so on.

Culture Method

The air-liquid interface method, matrix-overlaid method, and other advanced culture methods can be applied to organoid production.

Organoids Characterization

We perform cytomorphology, immunophenotype, and genomic analysis to explain how the established organoids resemble the original sarcoma and find differences in the model.

Technique Description
Phenotypic characterization
  • H&E staining
  • Immunohistochemistry
  • RT-PCR
  • Sarcoma tumor markers
  • Histological architecture
  • cytomorphology
  • Viability and proliferation
Phenotypic characterization
  • Whole genome sequencing
  • Whole exome sequencing
  • RNA sequencing
  • Somatic mutations (Indels, single nucleotide variants, and mutated cancer genes)
  • Copy number alterations
Tumorigenicity
  • Xenograft
  • Transplant organoids to NSG mouse/immunodeficient mouse
  • Evaluate tumor development

Subtypes of Sarcoma Cancer Organoids

Sarcoma contains over 200 histological subtypes that belong to two categories, soft tissue sarcomas, and un-soft tissue sarcomas. The organoid models include but are not limited to this.

Subtypes of Sarcoma Cancer Organoids
  • Epithelioid sarcoma organoid models
  • Osteosarcoma organoid models
  • Rhabdomyosarcoma organoid models
  • Gastrointestinal stromal tumors organoid models
  • Angiosarcomas organoid models
  • Leiomyosarcoma organoid models
  • Liposarcoma organoid models
  • Myxofibrosarcoma
  • Dermatofibrosarcoma protuberans organoid models
  • Pleiomorphic abdominal sarcoma organoid models

Application of Cancer Organoids to CAR-T Efficacy Tests

We provide CAR-T function assessment using versatile cancer organoids mediated T cell mechanism of action by various experiment assays.

Items Techniques
T cell migration towards organoids Trace by GFP reporter
T cell proliferation after recognition of organoid Trace by GFP reporter, immunostaining of cell subsets
Cytotoxicity IFNγ secretion, degranulation, LDH release
Organoids survival rate and loss of tumor antigen Fluorescent microscopy, RT-PCR, and flow cytometry analysis

Our Sarcoma Cancer Related CAR-T Products and Services

With extensive experience in CAR-T therapy development, Creative Biolabs provides sarcoma cancer-related products for antigen-targeted CAR-T construction and CAR-T cell-mediated cytotoxicity assay service using organoid models.

Target Antigen Description CAR-T Products
EGFRvIII EGFRvIII is a member of the epidermal growth factor receptor (EGFR) and has different expressions on soft tissue sarcomas, which may be a potential target for immunotherapy. Anti-EGFRvIII CAR-T
B7-H3 B7-H3 is demonstrated to express on osteosarcoma and serves as a promising target for a therapeutic strategy for bone cancer. Anti-B7-H3 CAR-T

Get in Touch with Us

Creative Biolabs offers faster development and enhanced cultures of organoids for CAR-T anti-tumor activity evaluation. Please contact us and get more detailed information.

Frequently Asked Questions

Q1. What are the advantages of a 3D organoid model?

What are the advantages of a 3D organoid model?Fig.2 Organoid is a physiological related model. (Fitzgerald, et al., 2021)

  • Retain patient-specific features of the tumor,
  • Present cell heterogeneity of tumor,
  • Recapitulate histological structure of tumor,
  • Easy to use and detect than in vivo model,
  • Connect the preclinical and clinical research,
  • The success rate of establishment is higher than the tumor cell line.

Q2. Why do patient-derived organoids and organoid xenografts show some difference in genomic features with initial patient tumors?

The differences between tumor tissue and organoid models may be related to the existence of multiple normal cell types in patient tumor tissues and the genetic alteration in organoids during long-term culturing.

References

  1. Forsythe, S.D.; et al. Patient-Specific Sarcoma Organoids for Personalized Translational Research: Unification of the Operating Room with Rare Cancer Research and Clinical Implications. Ann Surg Oncol. 2022, 29: 7354-7367.
  2. Wakamatsu, T.; et al. Establishment of Organoids From Human Epithelioid Sarcoma With the Air-Liquid Interface Organoid Cultures. Frontiers in oncology. 2022, 12: 893592.
  3. Fitzgerald, A.A.; et al. 3D Culture Systems for Exploring Cancer Immunology. Cancers. 2021, 13: 56.
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