CAR T cells: Building on the CD19 paradigm

2021/07/02 by Anat Globerson Levin, Isabelle Rivière, Zelig Eshhar +1 · 71 citations
Engineering · Immunology and Microbiology · Medicine · #Antigen #Biology #CAR-T cell therapy research #CD19 #Cancer immunotherapy #Cell biology #Chimeric antigen receptor #Immune Cell Function and Interaction #Immune system #Immunology #Immunotherapy #Major histocompatibility complex #Nanowire Synthesis and Applications #T cell

paper · pdf · doi:10.1002/eji.202049064

published in European Journal of Immunology 51(9), 2151-2163 (Wiley)

openalex publication_date 2021/07/02 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

Spearheaded by the therapeutic use of chimeric antigen receptors (CARs) targeting CD19, synthetic immunology has entered the clinical arena. CARs are recombinant receptors for antigen that engage cell surface molecules through the variable region of an antibody and signal through arrayed T-cell activating and costimulatory domains. CARs allow redirection of T-cell cytotoxicity against any antigen of choice, independent of MHC expression. Patient T cells engineered to express CARs specific for CD19 have yielded remarkable outcomes in subjects with relapsed/refractory B- cell malignancies, setting off unprecedented interest in T-cell engineering and cell-based cancer immunotherapy. In this review, we present the challenges to extend the use of CAR T cells to solid tumors and other pathologies. We further highlight progress in CAR design, cell manufacturing, and genome editing, which in aggregate hold the promise of generating safer and more effective genetically instructed immunity. Novel engineered cell types, including innate T-cell types, natural killer (NK) cells, macrophages, and induced pluripotent stem cell-derived immune cells, are on the horizon, as are applications of CAR T cells to treat autoimmunity, severe infections, and senescence-associated pathologies.

Citations

• Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19
• Utility of a safety switch to abrogate CD19.CAR T-cell–associated neurotoxicity

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• Catching Them Early: Framework Parameters and Progress for Prenatal and Childhood Application of Advanced Therapies. [europepmc]
• Role of CD19 Chimeric Antigen Receptor T Cells in Second-Line Large B Cell Lymphoma: Lessons from Phase 3 Trials. An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. [europepmc]
• Generation of T-cell-receptor-negative CD8αβ-positive CAR T cells from T-cell-derived induced pluripotent stem cells. [europepmc]
• Comparing Intraperitoneal and Intravenous Personalized ErbB2CAR-T for the Treatment of Epithelial Ovarian Cancer. [europepmc]
• Intestinal Microbiota: The Driving Force behind Advances in Cancer Immunotherapy. [europepmc]
• CAR T therapy extends its reach to autoimmune diseases. [europepmc]
• Multivalent adaptor proteins specifically target NK cells carrying a universal chimeric antigen receptor to ErbB2 (HER2)-expressing cancers. [europepmc]
• TET2 guards against unchecked BATF3-induced CAR T cell expansion. [europepmc]
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• CAR T-Cell Persistence Correlates with Improved Outcome in Patients with B-Cell Lymphoma. [europepmc]
• Targeting of chimeric antigen receptor T cell metabolism to improve therapeutic outcomes. [europepmc]
• Epitope-engineered human hematopoietic stem cells are shielded from CD123-targeted immunotherapy. [europepmc]
• Expanded Alternatives of CRISPR-Cas9 Applications in Immunotherapy of Colorectal Cancer. [europepmc]
• Disruption of SUV39H1-Mediated H3K9 Methylation Sustains CAR T-cell Function. [europepmc]
• Fine-tuning the antigen sensitivity of CAR T cells: emerging strategies and current challenges. [europepmc]
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• Preclinical Evaluation of Novel Folate Receptor 1-Directed CAR T Cells for Ovarian Cancer. [europepmc]
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