TY - JOUR
T1 - CRISPR Takes the Front Seat in CART-Cell Development
AU - Manriquez-Roman, Claudia
AU - Siegler, Elizabeth L.
AU - Kenderian, Saad S.
N1 - Funding Information:
SSK is an inventor on patents in the field of CAR immunotherapy that are licensed to Novartis (through an agreement between Mayo Clinic, University of Pennsylvania, and Novartis), to Mettaforge (through Mayo Clinic), and to Humanigen (through Mayo Clinic). SSK receives research funding from Kite, Gilead, Juno, Celgene, Novartis, Humanigen, MorphoSys, Tolero, Sunesis, Leahlabs, and Lentigen. These disclosures are not directly related to the content of this manuscript. CMR and ELS declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.
Funding Information:
This work was partly supported through the Mayo Clinic K2R pipeline (SSK), the Mayo Clinic Center for Individualized Medicine (SSK), and the Predolin Foundation (SSK).
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.
PY - 2021/3
Y1 - 2021/3
N2 - Chimeric antigen receptor T (CART)-cell immunotherapies have opened a door in the development of specialized gene therapies for hematological and solid cancers. Impressive response rates in pivotal trials led to the FDA approval of CART-cell therapy for certain hematological malignancies. However, autologous CART products are costly and time-intensive to manufacture, and most patients experience disease relapse within 1 year of CART administration. Additionally, CART-cell efficacy in solid tumors is extremely limited. CART-cell therapy is also associated with serious toxicities. Manufacturing difficulties, intrinsic T-cell defects, CART exhaustion, and treatment-associated toxicities are some of the current barriers to widespread adoption of CART-cell therapy. Genome editing tools such as CRISPR/Cas systems have demonstrated efficacy in further engineering CART cells to overcome these limitations. In this review, we will summarize the current approaches that use CRISPR to facilitate off-the-shelf CART products, increase CART-cell efficacy, and minimize CART-associated toxicities.
AB - Chimeric antigen receptor T (CART)-cell immunotherapies have opened a door in the development of specialized gene therapies for hematological and solid cancers. Impressive response rates in pivotal trials led to the FDA approval of CART-cell therapy for certain hematological malignancies. However, autologous CART products are costly and time-intensive to manufacture, and most patients experience disease relapse within 1 year of CART administration. Additionally, CART-cell efficacy in solid tumors is extremely limited. CART-cell therapy is also associated with serious toxicities. Manufacturing difficulties, intrinsic T-cell defects, CART exhaustion, and treatment-associated toxicities are some of the current barriers to widespread adoption of CART-cell therapy. Genome editing tools such as CRISPR/Cas systems have demonstrated efficacy in further engineering CART cells to overcome these limitations. In this review, we will summarize the current approaches that use CRISPR to facilitate off-the-shelf CART products, increase CART-cell efficacy, and minimize CART-associated toxicities.
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U2 - 10.1007/s40259-021-00473-y
DO - 10.1007/s40259-021-00473-y
M3 - Article
C2 - 33638865
AN - SCOPUS:85101835262
SN - 1173-8804
VL - 35
SP - 113
EP - 124
JO - BioDrugs
JF - BioDrugs
IS - 2
ER -