Optimizing CAR-T treatment: A T2EVOLVE guide to raw and starting material selection

Abstract

Chimeric antigen receptor (CAR)-T cell products, classified as Advanced Therapy Medicinal Products (ATMPs), have shown promising outcomes in cancer immunotherapy. The quality of raw and starting materials used in manufacturing is critical to ensure the efficacy and safety of CAR-T cell products and depends primarily on the selection of the right materials and the right suppliers. It is essential to consider a long-term strategy when selecting raw and starting materials to prevent delays in the supply of innovative, high-quality, and safe therapies to patients. A thorough assessment will allow developers not only to select suppliers who comply with regulatory requirements but also to ensure a sustainable supply of materials throughout the development and the commercial phases. A careful selection of materials and suppliers can avoid the need of comparability studies due to changes in the supply of materials, impacting costs and causing significant delays in development and treatment readiness for patients. This work, coordinated by the T²EVOLVE IMI consortium, provides guidance for the selection and handling of raw and starting materials. By following these suggestions, developers can ensure that they use high quality raw and starting materials through the product development and life cycle, resulting in safe and effective CAR-T therapies for patients.

Keywords: CAR-T cells; GMP; clinical trials; comparability; quality; raw material; stability; starting material; supplier selection; viral safety.

Graphical abstract

Figure 1

Starting material and raw material options for CAR-T cell products manufacturing processes The manufacturing processes for CAR-T cell products are divided into distinct phases, each of which requires a specific combination of raw materials (blue) and starting materials (green). The selection of these materials is of crucial importance with regard to the quality of the final CAR-T cell product.

Figure 2

Viral vector production at the Advanced Therapies Unit of the Immunotherapy Section of Immunology Service of the Hospital Clinic of Barcelona The production of lentiviral vectors carrying the expression cassette encoding an anti-CD19 CAR is initiated with the expansion and transfer of HEK293T cells (left), which are subsequently transfected with the corresponding plasmids by the addition of polyethyleneimine (PEI). Subsequently, the cell supernatant is collected and clarified, and the viral vector suspension is concentrated using tangential flow filtration and diafiltration (right).