Streamlining CAR T Cell Workflows with Automation

Automated counterflow centrifugation systems accelerate cell therapy workflow processes while maintaining cell yields and efficacy.

The Scientist Creative Services Team in collaboration with Thermo Fisher Scientific
Sep 7, 2021

Chimeric antigen receptor (CAR) T cells offer tremendous potential for cancer immunotherapy. These T cells express custom engineered T cell receptors (TCRs), allowing them to detect and attack cancer cells with greater efficacy and helping them avoid immune evasion mechanisms. Today, hundreds of clinical trials involving CAR T cells are in progress.

To manufacture CAR T cells, scientists first need to extract whole blood from either the patient being treated (autologous) or from a separate donor (allogeneic). Following this, they fraction the blood based on relative density through a process called leukapheresis, allowing the T cells to be separated and extracted. The collected T cells are expanded and transduced with the genetic material encoding CARs, then (re)-introduced to the patient.

This process can be laborious and complex, involving multiple steps, processes, and instruments. It requires care and consistency to make sure that contaminants do not enter the collected sample and that environmental disruptions do not affect cell phenotypes. As such, researchers have been searching for ways to streamline the CAR T cell production workflow. Streamlining will offer better accessibility and efficacy, and it will help ensure a more uniform and better quality end product.

Streamlining cell therapy workflows involves incorporating two key elements: closed systems and automation. These elements minimize the need for operator interventions and optimize protection against contamination and variability. Scientists and engineers are working together to design novel systems with these ideas in mind. The GibcoTM Cell Therapy Systems (CTSTM) RoteaTM Counterflow Centrifugation System is a compact processing system that uses single-use closed system kits for cell therapy and CAR T cell production workflows. With an adjustable flow rate ranging between 5 and 160 ml/min, the Gibco CTS Rotea processes cells in a fraction of the time required by manual workflows. Crucially, it can output volumes as low as 5 ml, making it possible to collect samples with cellular concentrations as high as 300 million/ml.

New instruments like the Gibco CTS Rotea come equipped with powerful user-friendly software to give researchers precise control over their experiments, letting them fine-tune protocol parameters, simulate protocols, and even evaluate process performance after runs. Beyond this, the Gibco CTS Rotea system is compatible with 21 CFR Part 11 data transmission and storage regulatory requirements, as it can communicate with compliant systems using OPC-UA protocols. The software can even toggle between R&D and manufacturing pre-set operator modes, making it ideal for both research and small-scale production applications.

These systems can handle both T cell workflows and applications involving other cells. For example, a direct comparison revealed that an automated workflow run using the Gibco CTS Rotea system matched manual Ficoll-based techniques in terms of T cell recovery and viability without affecting phenotype ratio and expansion capability. Additionally, Gibco CTS Rotea-automated processes outperformed Ficoll-based extraction methods when it came to general leukocyte extraction from whole blood.

The importance and prominence of CAR T cells in immuno-oncology will only grow in the future. This highlights the need for faster and more reliable means of CAR T cell production, whether for research or therapeutic use. The importance of automated closed production systems like the Gibco CTS Rotea Counterflow Centrifugation System at every stage of the production workflow has never been more apparent.