TY - JOUR
T1 - Enhancing CAR T cell efficacy
T2 - the next step toward a clinical revolution?
AU - Namuduri, Manjusha
AU - Brentjens, Renier J.
N1 - Publisher Copyright:
© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2020/5/3
Y1 - 2020/5/3
N2 - Introduction: The field of immunotherapy has witnessed considerable progress over the last two decades. Beginning with the ability to conceptualize CAR T cell therapy as immunotherapeutic approach, to effortlessly genetically modifying T cells, we have now reached the stage of mass production for clinical needs, all within less than quarter of a century. Areas covered: CAR T cell therapy has been tremendously successful in acute leukemia patients, specifically even in relapsed/refractory disease states. However, similar success is yet to be realized in other malignancies. This review article covers the challenges encountered with the current CD19-targeted CARs, as well as specific obstacles faced by adoptive therapy in solid tumors. It also discusses various strategies to counteract these problems. Expert opinion: CD19-directed trials in the past decade have exposed vulnerabilities in the current CAR T cell design, particularly concerning safety aspects, antigen escape, and T cell persistence. Building on these lessons and factoring in the unique challenges associated with immunotherapy in solid tumors will help generate CARs designed for future trials. Also, research related to the production of allogeneic CAR T cell products will boost the patient reach of this unique technology and possibly reduce financial burden.
AB - Introduction: The field of immunotherapy has witnessed considerable progress over the last two decades. Beginning with the ability to conceptualize CAR T cell therapy as immunotherapeutic approach, to effortlessly genetically modifying T cells, we have now reached the stage of mass production for clinical needs, all within less than quarter of a century. Areas covered: CAR T cell therapy has been tremendously successful in acute leukemia patients, specifically even in relapsed/refractory disease states. However, similar success is yet to be realized in other malignancies. This review article covers the challenges encountered with the current CD19-targeted CARs, as well as specific obstacles faced by adoptive therapy in solid tumors. It also discusses various strategies to counteract these problems. Expert opinion: CD19-directed trials in the past decade have exposed vulnerabilities in the current CAR T cell design, particularly concerning safety aspects, antigen escape, and T cell persistence. Building on these lessons and factoring in the unique challenges associated with immunotherapy in solid tumors will help generate CARs designed for future trials. Also, research related to the production of allogeneic CAR T cell products will boost the patient reach of this unique technology and possibly reduce financial burden.
KW - CAR
KW - CAR T cells
KW - Chimeric antigen therapy
KW - immunotherapy
KW - next steps in adoptive immunotherapy
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U2 - 10.1080/17474086.2020.1753501
DO - 10.1080/17474086.2020.1753501
M3 - Review article
C2 - 32267181
AN - SCOPUS:85084370500
SN - 1747-4086
VL - 13
SP - 533
EP - 543
JO - Expert Review of Hematology
JF - Expert Review of Hematology
IS - 5
ER -