An official website of the United States government
The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before
sharing sensitive information, make sure you’re on a federal
government site.
The site is secure.
The https:// ensures that you are connecting to the
official website and that any information you provide is encrypted
and transmitted securely.
1 Department of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 People's Republic of China.
2 Division of Periodontology, Diagnostic Sciences & Dental Hygiene, and Division of Biomedical Sciences, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA USA.
1 Department of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 People's Republic of China.
2 Division of Periodontology, Diagnostic Sciences & Dental Hygiene, and Division of Biomedical Sciences, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA USA.
Chimeric antigen receptor redirected T cells (CAR-T cells) have achieved inspiring outcomes in patients with B cell malignancies, and are now being investigated in other hematologic malignancies and solid tumors. CAR-T cells are generated by the T cells from patients' or donors' blood. After the T cells are expanded and genetically modified, they are reinfused into the patients. However, many challenges still need to be resolved in order for this technology to gain widespread adoption. In this review, we first discuss the structure and evolution of chimeric antigen receptors. We then report on the tools used for production of CAR-T cells. Finally, we address the challenges posed by CAR-T cells.
Structure of chimeric antigen receptor (CAR). The CAR includes ectodomain, transmembrane domain and…
Fig. 1
Structure of chimeric antigen receptor (CAR). The CAR includes ectodomain, transmembrane domain and endodomain
Fig. 2
Evolution of chimeric antigen receptor…
Fig. 2
Evolution of chimeric antigen receptor (CAR) from the first generation to the fourth…
Fig. 2
Evolution of chimeric antigen receptor (CAR) from the first generation to the fourth generation. Single chain antibody (CD3ζ or FcεRIγ) links the ITAM at transmembrane region for the first generation. Costimulatory molecule (CM1), such as CD28, has been engineered to the signal transduction region for the second generation. Another costimulatory molecule (CM2) based on the second generation for the third generation has been engineered to the signal transduction region, such as combining CD134 or CD137. The interleukin-12 (IL-12) based on the second generation for the fourth generation has been engineered to the signal transduction region. ITAM: Immunoreceptor tyrosine-based activation motifs
Ramos CA, Dotti G. Chimeric antigen receptor (CAR)-engineered lymphocytes for cancer therapy. Expert Opin Biol Ther. 2011;11(7):855–873. doi: 10.1517/14712598.2011.573476.
-
DOI
-
PMC
-
PubMed
Lipowska-Bhalla G, Gilham DE, Hawkins RE, Rothwell DG. Targeted immunotherapy of cancer with CAR T cells: achievements and challenges. Cancer Immunol Immunother. 2012;61(7):953–962. doi: 10.1007/s00262-012-1254-0.
-
DOI
-
PMC
-
PubMed
Liu J, Zhong JF, Zhang X, Zhang C. Allogeneic CD19-CAR-T cell infusion after allogeneic hematopoietic stem cell transplantation in B cell malignancies. J Hematol Oncol. 2017;10(1):35. doi: 10.1186/s13045-017-0405-3.
-
DOI
-
PMC
-
PubMed
Tasian SK, Gardner RA. CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL) Ther Adv Hematol. 2015;6(5):228–241. doi: 10.1177/2040620715588916.
-
DOI
-
PMC
-
PubMed
Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A. 1989;86(24):10024–10028. doi: 10.1073/pnas.86.24.10024.
-
DOI
-
PMC
-
PubMed