Current status and perspectives of chimeric antigen receptor modified T cells for cancer treatment
Authors:
Open Access
- 2 May 2017
- journal article
- review article
- Published by Oxford University Press (OUP) in Protein & Cell
- Vol. 8 (12) , 896-925
Abstract
Chimeric antigen receptor (CAR) is a recombinant immunoreceptor combining an antibody-derived targeting fragment with signaling domains capable of activating cells, which endows T cells with the ability to recognize tumor-associated surface antigens independent of the expression of major histocompatibility complex (MHC) molecules. Recent early-phase clinical trials of CAR-modified T (CAR-T) cells for relapsed or refractory B cell malignancies have demonstrated promising results (that is, anti-CD19 CAR-T in B cell acute lymphoblastic leukemia (B-ALL)). Given this success, broadening the clinical experience of CAR-T cell therapy beyond hematological malignancies has been actively investigated. Here we discuss the basic design of CAR and review the clinical results from the studies of CAR-T cells in B cell leukemia and lymphoma, and several solid tumors. We additionally discuss the major challenges in the further development and strategies for increasing anti-tumor activity and safety, as well as for successful commercial translation.Keywords
This publication has 201 references indexed in Scilit:
- TanCAR: A Novel Bispecific Chimeric Antigen Receptor for Cancer ImmunotherapyMolecular Therapy Nucleic Acids, 2013
- T Cells Targeting Carcinoembryonic Antigen Can Mediate Regression of Metastatic Colorectal Cancer but Induce Severe Transient ColitisMolecular Therapy, 2011
- Is It Safer CARs That We Need, or Safer Rules of the Road?Molecular Therapy, 2010
- Antitransgene Rejection Responses Contribute to Attenuated Persistence of Adoptively Transferred CD20/CD19-Specific Chimeric Antigen Receptor Redirected T Cells in HumansTransplantation and Cellular Therapy, 2010
- Treatment of Chronic Lymphocytic Leukemia With Genetically Targeted Autologous T Cells: Case Report of an Unforeseen Adverse Event in a Phase I Clinical TrialMolecular Therapy, 2010
- Case Report of a Serious Adverse Event Following the Administration of T Cells Transduced With a Chimeric Antigen Receptor Recognizing ERBB2Molecular Therapy, 2010
- Chimeric Antigen Receptors Combining 4-1BB and CD28 Signaling Domains Augment PI3kinase/AKT/Bcl-XL Activation and CD8+ T Cell–mediated Tumor EradicationMolecular Therapy, 2010
- Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastomaNature Medicine, 2008
- ERBB receptors and cancer: the complexity of targeted inhibitorsNature Reviews Cancer, 2005
- The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissuesSeminars in Cancer Biology, 1999