CAR-T Cell Therapies From the Transfusion Medicine Perspective

Abstract

The use of chimeric antigen receptor (CAR)-T cell therapy for the treatment of hematologic malignancies has generated significant excitement over the last several years. From a transfusion medicine perspective, the implementation of CAR-T therapy as a potential mainstay treatment for not only hematologic but also solid-organ malignancies represents a significant opportunity for growth and expansion. In this review, we will describe the rationale for the development of genetically redirected T cells as a cancer therapeutic, the different elements that are required to engineer these cells, as well as an overview of the process by which patient cells are harvested and processed to create and subsequently validate CAR-T cells. Finally, we will briefly describe some of the toxicities and clinical efficacy of CAR-T cells in the setting of patients with advanced malignancy.

Keywords: Adoptive immunotherapy; Cell processing; Gene transfer; Leukapheresis; T cells.

Figure 1

Design of chimeric antigen receptors.

Figure 2

Peripheral blood separation via leukapheresis.

Figure 3

Cell separation by elutriation and antibody-bead conjugate selection. a. Elutriation begins with the introduction of a heterogeneous cell population into the elutriation chamber. i. Centrifugal force, applied to the cells by spinning the chamber, begins to separate cell populations based on density. ii. Buffer is introduced counter to the direction of centrifugal force. Counter flow buffer separates cells by size and density. iii. The separated cell populations can be sequentially removed in fractions to obtain enriched final cell populations. While certain cell types are typically found in specific fractions, a variety of factors influence which fractions contain target cell populations. b. i. Antibody-bead conjugate selection also begins with a heterogeneous cell population. ii. A monoclonal antibody-magnetic bead conjugate is applied to the cells, coating the target cell population. iii. The cells are then placed in a magnetic field as they flow through a semi-porous column. iv. Non-coated cells are separated as waste. v. The column can then be removed from the magnetic field and flushed to obtain an enriched cell population. This approach can be used to depletion undesirable cell populations as well, in which case the flow through cells would be retained.