TY - JOUR
T1 - Reprint of
T2 - Building a Safer and Faster CAR: Seatbelts, Airbags, and CRISPR
AU - Perales, Miguel Angel
AU - Kebriaei, Partow
AU - Kean, Leslie S.
AU - Sadelain, Michel
N1 - Publisher Copyright:
© 2018
PY - 2018/3
Y1 - 2018/3
N2 - Therapeutic T cell engineering has recently garnered widespread interest because of the success of CD19 chimeric antigen receptor (CAR) therapy. CARs are synthetic receptors for antigen that redirect the specificity and reprogram the function of the T cells in which they are genetically introduced. CARs targeting CD19, a cell surface molecule found in most leukemias and lymphomas, have yielded high remission rates in patients with chemorefractory, relapsed disease, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. The toxicities of this treatment include B cell aplasia, cytokine release syndrome (CRS), and neurotoxicity. Although reversible in most instances, these toxicities may require specific medical interventions, including transfer to intensive care to treat severe CRS. Guidelines for managing these toxicities are emerging. The recent report of a nonhuman primate model for CRS is poised to help advance the management of this syndrome. Finally, new engineering modalities, based on the use of targeted nucleases like CRISPR, may further enhance the efficacy and safety of CAR T cells.
AB - Therapeutic T cell engineering has recently garnered widespread interest because of the success of CD19 chimeric antigen receptor (CAR) therapy. CARs are synthetic receptors for antigen that redirect the specificity and reprogram the function of the T cells in which they are genetically introduced. CARs targeting CD19, a cell surface molecule found in most leukemias and lymphomas, have yielded high remission rates in patients with chemorefractory, relapsed disease, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. The toxicities of this treatment include B cell aplasia, cytokine release syndrome (CRS), and neurotoxicity. Although reversible in most instances, these toxicities may require specific medical interventions, including transfer to intensive care to treat severe CRS. Guidelines for managing these toxicities are emerging. The recent report of a nonhuman primate model for CRS is poised to help advance the management of this syndrome. Finally, new engineering modalities, based on the use of targeted nucleases like CRISPR, may further enhance the efficacy and safety of CAR T cells.
KW - Adoptive T cell therapy
KW - Adoptive immunotherapy
KW - CART
KW - Chimeric antigen receptor T cells
KW - Cytokine release syndrome
KW - Hematopoietic stem cell transplantation
KW - Immunotherapy
KW - Neurologic Toxicity
UR - http://www.scopus.com/inward/record.url?scp=85044862804&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044862804&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2017.12.789
DO - 10.1016/j.bbmt.2017.12.789
M3 - Review article
C2 - 29425516
AN - SCOPUS:85044862804
SN - 1083-8791
VL - 24
SP - S15-S19
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 3
ER -