Mitochondrial Oxidative Metabolism Analysis of Tumor-infiltrating CAR-T Cells

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

Background

Human solid tumors have higher levels of hypoxia than the normal tissues from which they arose. The observed decreased oxygen level was linked to tumor cells' increased resistance to antitumor treatment as well as tumor metastases. Hypoxia in the tumor microenvironment is another important factor limiting the efficacy of CAR-T cells in the treatment of solid tumors. Hypoxia inhibits T cell differentiation to memory phenotypes by reducing CAR-T cell proliferation.

Mitochondrial metabolic pathways play critical roles in CAR-T cell fate, function, and persistence. Creative Biolabs provides preclinical in vivo mitochondria metabolism studies of CAR-T in animal models, providing valuable information for later clinical applications.

Fig. 1 Mitochondrial biogenesis in CAR-T cells of CR, PR patients, and NR leukemia patients.¹

Our Services

Creative Biolabs provides CAR-T cell mitochondrial dynamics analysis to characterize oxidative metabolism and provide clients with a better understanding of the effects of engineered T cells.

Workflow

Tumor-infiltrating CAR-T Cells Isolation and Identification

In our assay, we use a variety of biomarkers to characterize TIL CAR-T cells, such as activation, inhibition ligand, CAR expression, immune phenotype, and so on.

Fig. 2 Tumor-infiltrating CAR-T Cells Isolation and Identification workflow.

Mitochondrial Dynamics Analysis

OCR and ECAR

The high-quality commercial kits are used to assess the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), which are major indicators of mitochondrial respiration and glycolysis, respectively, and these measurements provide a systems-level view of cellular metabolic function.

Energy Metabolism

The relative ATP levels, as well as the basal and maximal respiratory capacities, are measured after decoupling the mitochondrial membrane with FCCP.

Number and Morphology of Mitochondria

The transmission electron microscope can also detect changes in the number and morphology of mitochondria as an indicator of increased mitochondrial formation and oxidative metabolism in CAR-T cells.

Mechanism of Mitochondrial Metabolism

Advanced single-cell analysis technologies provide us with a variety of tools for studying the mechanism of CAR-T energy metabolism. We offer mitochondrial oxidative metabolism analysis in a variety of associated biomarkers and mRNA expression levels.

Mechanism of Mitochondrial Metabolism

Related CAR-T Products and Services

Creative Biolabs is a pioneer in CAR-T therapy development, offering commercial immune cell products as well as one-stop CAR-T cell development services for tumor-infiltrating CAR-T cells and mitochondrial oxidative metabolism studies in cells.

One-stop CAR-T Development Service

Our robust cell therapy platform includes biomarker identification, scFv generation, CAR design and construction, high titter viral particles production.

CAR-T In Vivo Assays

Patient derived xenograft animal models, including mouse and non-primate animal, are used for in vivo safety and efficacy evaluations. Tumor-infiltrating CAR-T cells can be isolated from tumors for further studies.

Fig. 3 Representative OCR and ECAR curves and glycolysis stress test at different metabolic states of CAR-T cells.²

We are delighted to share our extensive knowledge of the mitochondrial oxidative metabolism of tumor-infiltrating CAR-T cells with our clients. Creative Biolabs scientists will design the best assay for your objectives and budget, saving you time from laborious technical procedures. Please contact us so that we can provide you with a customized research service.

References

Rostamian, Hosein, et al. "Mitochondria as Playmakers of CAR T-cell Fate and Longevity." Cancer Immunology Research 9.8 (2021): 856-861.
Cao, Bihui, et al. "Remodelling of tumour microenvironment by microwave ablation potentiates immunotherapy of AXL-specific CAR-T cells against non-small cell lung cancer." Nature Communications 13.1 (2022): 6203.