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Real-time Monitoring of Mitochondrial Respiration in Cytokine-differentiated Human Primary T Cells

Real-time Monitoring of Mitochondrial Respiration in Cytokine-differentiated Human Primary T Cells

Published on: October 19, 2021

Improved CAR-T cell activity associated with increased mitochondrial function primed by galactose.

Golda Gross^1,2, Suha Alkadieri^1,2, Amilia Meir¹

¹Cell Therapy Lab, Sheba Medical Center, Tel Hashomer, Israel.

|May 7, 2024

Summary

Enhancing CAR-T cell metabolism with galactose improves mitochondrial function and boosts efficacy in leukemia models. This metabolic shift offers a promising strategy to overcome CAR-T cell relapse in cancer therapy.

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Area of Science:

Immunology
Cellular Metabolism
Cancer Therapy

Background:

Chimeric antigen receptor T-cell (CAR-T) therapy shows promise for B-cell malignancies but often faces long-term relapse.
Interventions to improve CAR-T cell products frequently investigate their metabolic state.

Purpose of the Study:

To assess the impact of cellular metabolism on the efficacy of CD19 CAR-T cells in acute lymphoblastic leukemia.
To investigate if altering the carbon source in cell culture media can enhance CAR-T cell function.

Main Methods:

Analysis of clinical CD19-28z CAR-T cell products from acute lymphoblastic leukemia patients.
Comparison of CAR-T cells cultured in glucose-based versus galactose-based media.
Assessment of mitochondrial function (oxygen consumption rate) and in vitro/in vivo efficacy.

Main Results:

CAR-T cells associated with complete response exhibited higher mitochondrial function.
Galactose-based media significantly increased CAR-T cell mitochondrial activity and in vitro efficacy.
Galactose-primed CAR-T cells demonstrated improved leukemia-free survival in an in vivo mouse model.

Conclusions:

Mitochondrial metabolism is a critical determinant of CAR-T cell efficacy.
Switching the carbon source to galactose represents a translational strategy to enhance clinical CAR-T cell products and overcome relapse.