Recent Advances in Allogeneic CAR-T Cells

Abstract

In recent decades, great advances have been made in the field of tumor treatment. Especially, cell-based therapy targeting tumor associated antigen (TAA) has developed tremendously. T cells were engineered to have the ability to attack tumor cells by generating CAR constructs consisting of genes encoding scFv, a co-stimulatory domain (CD28 or TNFRSF9), and CD247 signaling domains for T cell proliferation and activation. Principally, CAR-T cells are activated by recognizing TAA by scFv on the T cell surface, and then signaling domains inside cells connected by scFv are subsequently activated to induce downstream signaling pathways involving T cell proliferation, activation, and production of cytokines. Many efforts have been made to increase the efficacy and persistence and also to decrease T cell exhaustion. Overall, allogeneic and universal CAR-T generation has attracted much attention because of their wide and prompt usage for patients. In this review, we summarized the current techniques for generation of allogeneic and universal CAR-T cells along with their disadvantages and limitations that still need to be overcome.

Immunotherapy and Its Development for Gynecological (Ovarian, Endometrial and Cervical) Tumors: From Immune Checkpoint Inhibitors to Chimeric Antigen Receptor (CAR)-T Cell Therapy

“…Recently, a fifth CAR generation was conceived: it is fairly similar to that of the fourth generation in terms of molecular structure (including CD3ζ, and CD28 as a costimulatory molecule, which enhances the secretion of proinflammatory cytokines), with the insertion of an intracellular domain of IL2RB chain fragment (or another similar receptor). This latter fragment was added to bind STAT3, which is responsible for cell proliferation, preventing terminal differentiation and ensuring CAR persistence [ 77 ]. Within this context, it is also possible to transplant these cells from healthy donors by knocking-out HLA and TCR genes to avoid graft-versus-host disease and to use the therapy for more than one patient [ 78 ].…”

Chimeric Antigen Receptor Based Therapy as a Potential Approach in Autoimmune Diseases: How Close Are We to the Treatment?

“…In contrast, TCR requires peptide processing in the MHC-dependent manner to identify cells with particular human leukocyte antigen (HLA) expression (25,26). A typical CAR is composed of three major components, including ectodomain consisting of an antigen-recognition domain and a hinge domain, a transmembrane domain, and endodomain defined in co-stimulatory(s) and an intracellular signaling domain ( Figure 1A) (27)(28)(29).…”

Best practices for the development, analytical validation and clinical implementation of flow cytometric methods for chimeric antigen receptor T cell analyses

“…At a minimum, the CAR T cell product characterization panel would include a viability dye, the CAR detection reagent, CD3, CD4, CD8, CD14, CD19 and CD56 to enumerate other cell types including monocytes, B‐cells and NK cells in addition to CAR positive CD4 or CD8 T cells. Note that for allogeneic CAR T cell products, presence of CD3+ or T cell receptor (TCR) + cells in the final product would represent a contaminant since by design their endogenous TCR is knocked out (Kim & Cho, 2020).…”

“…Strategies for critical reagent characterization and tracking approaches have been described earlier (Piccoli et al, 2019). Note that for allogeneic CAR T cell products, presence of CD3+ or T cell receptor (TCR) + cells in the final product would represent a contaminant since by design their endogenous TCR is knocked out (Kim & Cho, 2020).…”