Providing the Starting Material to the Manufacturer of an Approved and Commercially Available Autologous CAR-T Cell Treatment

Abstract

CAR-T cell manufacturing starts from a collection of mononuclear cells (MNCs, although specifically only T lymphocytes will be used for the preparation) from the patient using apheresis. Although several initiatives are working on the development of allogeneic CAR-T cells, currently only CAR-T therapies of autologous origin are approved in the European Union. The present chapter only discusses already or soon-to-be marketed autologous CAR-T cells and excludes investigational CAR-T cells or rare CAR-T cells approved in the context of hospital exemption, such as the ARI-001 product (Ortiz-Maldonado et al. 2021); on this topic, please refer to Chapter 3c.

Get Off on the Right Foot: How to Plan an Efficient Leukocytapheresis to Collect T Cells for CAR T-Cell Manufacturing

“…As stated before, detailed information about how to proceed to collect cells as a raw material for CAR T-cell manufacturing is not available in some protocols [ 16 ]. At least, the desired number of cells to be collected must be specified in the protocol [ 17 ].…”

“…Estimating the volume to be processed based on the calculation of the CE is usually the most widely used and, therefore, the most validated approximation [ 24 , 26 , 28 , 30 ]. We detail, in the following two sections, current workload in our institution when a patient is admitted to collect MNCs as a starting material for CAR T-cell manufacturing [ 16 ].…”

“…This point is crucial to reduce as much as possible the time between decision of CAR T-cell therapy and its final administration. During the pre-apheresis visit, we, as other authors do, recommend a checklist [ 16 ].…”

“…Believe it or not, although obtaining T cells from patients is the first step in this complex process, little attention has been paid to this issue, and no guidelines or recommendations have been made until recently [ 10 , 11 , 12 , 13 , 14 , 15 ]. In fact, a detailed leukocytapheresis collection manual, with all requirements of the collection process, is not available in some protocols [ 16 ]. Table 1 presents data regarding different requirements for cell collection as starting material for CAR T-cell therapy [ 16 ].…”

“…In fact, a detailed leukocytapheresis collection manual, with all requirements of the collection process, is not available in some protocols [ 16 ]. Table 1 presents data regarding different requirements for cell collection as starting material for CAR T-cell therapy [ 16 ]. The aim of the present review was to give readers with a list of criteria that are necessary to include in a collection manual before starting leukocytapheresis as well as a list of considerations for collection parameters in order to customize the apheresis procedures to adult donors and to collect cells in an efficient and safe way.…”