An Analysis of Monitoring Solutions for CAR T Cell Production

Abstract

The chimeric antigen receptor T cell (CAR T) therapy has shown remarkable results in treating certain cancers. It involves genetically modifying a patient's T cells to recognize and attack cancer cells. Despite its potential, CAR T cell therapy is complex and costly and requires the integration of multiple technologies and specialized equipment. Further research is needed to achieve the maximum potential of CAR T cell therapies and to develop effective and efficient methods for their production. This paper presents an overview of current measurement methods used in the key steps of the production of CAR T cells. The study aims to assess the state of the art in monitoring solutions and identify their potential for online monitoring. The results of this paper contribute to the understanding of measurement methods in CAR T cell manufacturing and identify areas where on-line monitoring can be improved. Thus, this research facilitates progress toward the development of effective monitoring of CAR T cell therapies.

Keywords: CAR T cell therapy; advanced therapy medicinal product (ATMP); monitoring; on‐line measurement.

FIGURE 1

The increase and convergence of the three entities automation, digitalization, and monitoring leading to the concept of Pharma 4.0.

FIGURE 2

The procedure for generating allogeneic CAR T cells from the hospital into the laboratory and back to the hospital. There, the cells are transformed into CAR T cells and subsequently returned to the hospital for transfusion to the patient. Image adapted from [2].

FIGURE 3

Various methods of analysis. Off‐line measurements require collecting samples and conducting laboratory analysis. At‐line measurements bring the laboratory to the process site but still require sample collection. On the other hand, on‐line and in‐line methods involve direct analysis. In on‐line measurements, slipstream techniques like bypasses are needed, while in‐line measurement is directly integrated. Illustration based on [49, 50].