CAR-T-cell-therapies

Circle Oncodesign Services

Evaluating your CAR-T cel based-therapies with an experienced CRO in immuno-oncology

 

 

What is a CAR-T cell therapy ?

CAR-T (Chimeric Antigen Receptor – T) cell therapy is a cellular immunotherapy which aims to fight cancer by relying on the patient’s own immune system. CAR-T cells constitute a new approach to cancer treatment based on taking immune cells from a patient, modifying them genetically and reinjecting them into the patient. Unlike traditional cancer therapies, CAR-T cell therapy is considered as a “living drug” and personalized therapy.

 

 

Basics of the CAR-T cell therapy process 

First, T-cells are isolated from the blood of the patient. Then, T-cells are transduced using genetic engineering techniques with a chimeric antigen receptor gene to create “CAR-T cells”. The cells are cultured and expanded in vitro to obtain adequate numbers of cells for infusion. 

Following this, high-quality CAR-T cells are infused into the patient to target and kill cancer cells while avoiding damage to normal tissues. 

Improved understanding of the interaction between CAR-T cells and tumors

To enhance the understanding of interactions between CAR-T cells and tumors, different analytical strategies can be used in Drug Discovery. Please find below some examples.

1

Imaging Tools

Advanced imaging technologies such as live-cell imaging, multiphoton microscopy, or positron emission tomography (PET) allow to visualize real-time interactions at a cellular level. With bioluminescence or fluorescence imaging tools, CAR-T cell dynamics and distribution can be monitored within live organisms. 

2

Single-Cell analysis

Single-cell RNA sequencing and proteomics analyze individual cells, providing insights into the heterogeneity of the CAR-T cell responses within the tumor microenvironment. 

3

3D Tumor Models

Three-dimensional tumor models or organoids mimic the complexity of the in vivo tumor microenvironment, allowing for more accurate representations of CAR-T cell interactions. 

4

Integration of Computational Models

The combination of experimental data with computational models allows to simulate and predict the dynamics of CAR-T cell interactions, aiding in the interpretation of complex biological processes. 

5

Biomarker Identification

Identifying and validating biomarkers associated with effective CAR-T cell responses or resistance, enables better patient stratification and personalized treatment approaches. 

6

Patient-Derived Models

Incorporating patient-derived tumor samples to create models that reflect the unique characteristics of individual tumors, facilitates a more personalized understanding of CAR-T cell interactions. 

 

Advanced imaging technologies such as live-cell imaging, multiphoton microscopy, or positron emission tomography (PET) allow to visualize real-time interactions at a cellular level. With bioluminescence or fluorescence imaging tools, CAR-T cell dynamics and distribution can be monitored within live organisms. 

Single-cell RNA sequencing and proteomics analyze individual cells, providing insights into the heterogeneity of the CAR-T cell responses within the tumor microenvironment. 

Three-dimensional tumor models or organoids mimic the complexity of the in vivo tumor microenvironment, allowing for more accurate representations of CAR-T cell interactions. 

The combination of experimental data with computational models allows to simulate and predict the dynamics of CAR-T cell interactions, aiding in the interpretation of complex biological processes. 

Identifying and validating biomarkers associated with effective CAR-T cell responses or resistance, enables better patient stratification and personalized treatment approaches. 

Incorporating patient-derived tumor samples to create models that reflect the unique characteristics of individual tumors, facilitates a more personalized understanding of CAR-T cell interactions. 

 

By employing these strategies, researchers can gain a deeper understanding of the intricate interactions between CAR-T cells and tumors, ultimately contributing to the refinement and improvement of CAR-T cell therapies.

 

Oncodesign Services offers a high experience in CAR-T cell therapy development

Oncodesign Services contributes to this revolutionary field by helping biotechs and pharmaceutical companies evaluate their CAR-T cell based-therapies.  Our in vitro and in vivo immuno-oncology platforms allow us to bring essential data together to validate new therapies.  

Our capabilities in supporting CAR-T cell research include: 

  • CAR-T cell design
  • CRISP-R cas-9 gene editing
  • Primary T-cell in vitro assays
    • Human PBMCs isolation, sorting
    • Cytotoxicity assays with co-cultured cancer cells
    • Proliferation
    • Cytokine profiles
  • Efficacy studies
  • Ex-vivo immuno-phenotyping of TILs
  • In vivo models including PDX and humanized mouse models
  • Preclinical evaluation
    • In vivo proliferation of effector cells: CAR expression and CFSE assay
    • Xenograft tumor growth inhibition (NOG-SCID mice)
    • Survival as endpoint
    • Whole animal imaging — Biodistribution
  • Biorepositories
    • We collaborate with multiple local and national medical centers for healthy donor and patient’ samples (blood, tissues)
    • We currently bank >200 ready to use healthy donor PBMCs

In vivo models for CAR-T cell therapies

Oncodesign Services has a vast experience with the humanization of mice to support the study of CAR-T cells and other immuno-modulatory therapies requiring a human immune system.  Our laboratories began using humanized animals in 2002, making us a pioneer in the early days of commercial adoption. 

We developed many humanized models to test compounds that activate immune cells to lyse tumor cells. This represents the ideal starting point for the many companies who are developing and would like to test CAR-T cell and checkpoint inhibitor therapies today. 

“Tumors are constantly adapting to evade the immune system. CAR-T is like an education, because the tumor cells send some messages to the immune system to say, ‘I’m your friend, so don’t attack me’,” explains Duchamp. “We try to terminate this communication and say, ‘No, tumor cells are not your friend.’”

Olivier DUCHAMP – Head of translational pharmacology department at Oncodesign Services

Our pharmacology department combines innovative imaging techniques and various tools providing in vivo information at the single-cell level to identify how various subpopulations of CAR T cells behave within the tumor microenvironment.

 

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