CAR T-Cell Therapy

Harnessing the immune system for cancer treatment has defined the past decade, with chimeric antigen receptor (CAR) T-cell therapy marking significant advancements in oncology. CAR T-cells are personalized immunotherapies engineered by extracting and then genetically modifying a patient’s own T-cells with enhanced specificity and killing efficacy towards the patient’s cancer cells. These cells are then reinjected into the host, where they aid in tumor clearance. They have transformed the treatment landscape for hematologic malignancies like leukemia, lymphoma, and myeloma, particularly for patients with limited effective therapeutic options.

Cancer therapies are useful only to those who can access them, and unfortunately, CAR T-cells are costly to produce because of their patient-specific nature and complex manufacturing process. Exploring novel manufacturing methods for CAR T-cells may help reduce costs and improve accessibility to these life-saving treatments.

Emory University’s Novel Approach to CAR T-Cell Manufacturing

One example of this exploration is seen in Emory University’s Wallace H. Coulter Department of Biomedical Engineering study published in Advanced Healthcare Materials utilizing 908 Devices’ REBEL at-line analyzer for cell nutritional and metabolic profiling in their quest to improve the potency and accessibility of CAR T-cell therapies.

While some patients initially respond well to CAR T-cell treatment, many relapsed, and refractory patients do not achieve durable complete responses (DCR). DCR is linked to CAR T-cell products containing memory phenotype T-cells, so it follows that consistently promoting memory phenotypes during CAR T-cell manufacturing can significantly improve therapeutic outcomes for patients.

The Emory team explored this insight by developing microbead libraries for T-cell activation for increased proportion of naïve phenotype T-cells. This novel modular multi-cytokine backpack (MCB) platform combines the signals necessary for activation, co-stimulation, and cytokine support into a single “all-in-one” reagent for CAR T-cell manufacturing. In their initial research, T-cells were activated ex vivo using a 50-compound microbead library.

Emory researchers used REBEL to test amino acid and vitamin concentrations in the final CAR T-cell product spent media. The CAR T-cells manufactured with multi-cytokine backpacks and identified as having desirable, long-lived T-cell phenotype markers, also showed metabolic differences to T-cells expected to be exhausted. The team noted lower levels of amino acids like alanine and higher levels of proline in the CAR T-cells linked to desirable phenotypes. These findings are promising, as amino acids are crucial media components for T-cell activation. By plotting the amino acid levels measured by REBEL with JMP software, 908 Devices add-in tool for data visualization, researchers determined the functionally superior MCBs.

Although amino acid analysis is not regularly performed as part of CAR T-cell experiments due to the complexity of many traditional analysis methods and sample volume limitations, the REBEL’s automated quantitation and low sample volume requirements (10uL) enabled rapid analysis at the bench side with no requirement for prior mass spec expertise.

Enhancing Cell Therapy Research & Development with 908 Devices

The research with Emory is just one example of how leveraging REBEL data can enhance understanding of CAR-T cell potency and longevity. This will ultimately lead to optimal manufacturing, delivering superior CAR T-cell products and making treatments more accessible to patients.

REBEL is a first-of-its-kind fresh and spent media analyzer that enables biopharma researchers to accelerate process development cycles and maximize bioreactor utilization by running media analysis at-line. It’s efficient, enables real-time data tracking (analyzes over 30 key media nutrients in under 10 minutes), small and simple to use.

To learn more about our work with Emory University, view this webinar: Engineering Functionally Improved CAR T cells with a Multi-Cytokine Backpack Platform with Insights into Metabolism and view this poster presented at the 2024 Advanced Manufacturing Cell and Gene Therapies Conference.

Cell Therapy

Learn more about how we are working to overcome manufacturing challenges in cell therapies.