TY - JOUR
T1 - CAR T cell therapy and the tumor microenvironment
T2 - Current challenges and opportunities
AU - Kankeu Fonkoua, Lionel A.
AU - Sirpilla, Olivia
AU - Sakemura, Reona
AU - Siegler, Elizabeth L.
AU - Kenderian, Saad S.
N1 - Funding Information:
S.S.K. is an inventor on patents in the field of CAR immunotherapy that are licensed to Novartis (through an agreement between the Mayo Clinic, University of Pennsylvania, and Novartis), and Mettaforge (through the Mayo Clinic). R.S. and S.S.K. are inventors on patents in the field of CAR immunotherapy that are licensed to Humanigen (through the Mayo Clinic). S.S.K. receives research funding from Kite , Gilead , Juno , Celgene , Novartis , Humanigen , MorphoSys , Tolero , Sunesis , Viracta , and Lentigen . S.S.K. has participated in scientific advisory boards with Kite, Gilead, Juno, BMS, Novartis, and Humanigen. S.S.K. is on the DSMB for Humanigen.
Funding Information:
This work was partly supported by grants from the Mayo Clinic Center for Individualized Medicine (to S.S.K.) and the Passano Foundation (to R.S. and S.S.K.). L.A.K.F. O.S. R.S. E.L.S. and S.S.K. wrote, edited, and approved the final version of the manuscript. S.S.K. is an inventor on patents in the field of CAR immunotherapy that are licensed to Novartis (through an agreement between the Mayo Clinic, University of Pennsylvania, and Novartis), and Mettaforge (through the Mayo Clinic). R.S. and S.S.K. are inventors on patents in the field of CAR immunotherapy that are licensed to Humanigen (through the Mayo Clinic). S.S.K. receives research funding from Kite, Gilead, Juno, Celgene, Novartis, Humanigen, MorphoSys, Tolero, Sunesis, Viracta, and Lentigen. S.S.K. has participated in scientific advisory boards with Kite, Gilead, Juno, BMS, Novartis, and Humanigen. S.S.K. is on the DSMB for Humanigen.
Funding Information:
This work was partly supported by grants from the Mayo Clinic Center for Individualized Medicine (to S.S.K.) and the Passano Foundation (to R.S. and S.S.K.).
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/6/16
Y1 - 2022/6/16
N2 - Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable outcomes in individuals with hematological malignancies, but its success has been hindered by barriers intrinsic to the tumor microenvironment (TME), particularly for solid tumors, where it has yet to make its mark. In this article, we provide an updated review and future perspectives on features of the TME that represent barriers to CART cell therapy efficacy, including competition for metabolic fuels, physical barriers to infiltration, and immunosuppressive factors. We then discuss novel and promising strategies to overcome these obstacles that are in preclinical development or under clinical investigation.
AB - Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable outcomes in individuals with hematological malignancies, but its success has been hindered by barriers intrinsic to the tumor microenvironment (TME), particularly for solid tumors, where it has yet to make its mark. In this article, we provide an updated review and future perspectives on features of the TME that represent barriers to CART cell therapy efficacy, including competition for metabolic fuels, physical barriers to infiltration, and immunosuppressive factors. We then discuss novel and promising strategies to overcome these obstacles that are in preclinical development or under clinical investigation.
KW - chimeric antigen receptor (CAR) T cell therapy
KW - immunosuppression
KW - metabolic fuels
KW - physical barriers
KW - tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85127483640&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85127483640&partnerID=8YFLogxK
U2 - 10.1016/j.omto.2022.03.009
DO - 10.1016/j.omto.2022.03.009
M3 - Review article
AN - SCOPUS:85127483640
SN - 2372-7705
VL - 25
SP - 69
EP - 77
JO - Molecular Therapy - Oncolytics
JF - Molecular Therapy - Oncolytics
ER -