TY - JOUR
T1 - Solid tumours: Building bridges to CAR-T success
AU - Maher, John
N1 - Funding Information:
This work was supported by Leucid Bio, the Jon Moulton Charity Trust, the Wellcome Trust, and the Experimental Cancer Medicine Centre at King's College London.
Publisher Copyright:
© 2023 The Authors. Clinical and Translational Discovery published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
PY - 2023/4
Y1 - 2023/4
N2 - Immunotherapy using chimeric antigen receptor (CAR)-engineered T-cells has achieved remarkable impact in the treatment of selected blood cancers. However, meaningful clinical efficacy against nonhaematological malignancies has largely proven elusive. In this minireview, the main challenges to successful CAR-based intervention against solid tumours are considered. Obstacles are considered in four categories, namely target selection, trafficking of CAR-engineered cells to tumour deposits, the need to overcome the physical, chemical and biological hurdles to immune effector function that operate within the tumour microenvironment and selection of the best host cells for CAR engineering. A range of pre-clinical technologies that have been developed in an effort to overcome these issues are also surveyed. Although clinical progress comes dropping slow, rapid and continued advances in cellular engineering and manufacture, coupled with the emergence of several complementary interventions bodes well for the future success of CAR T-cell immunotherapy of solid tumours.
AB - Immunotherapy using chimeric antigen receptor (CAR)-engineered T-cells has achieved remarkable impact in the treatment of selected blood cancers. However, meaningful clinical efficacy against nonhaematological malignancies has largely proven elusive. In this minireview, the main challenges to successful CAR-based intervention against solid tumours are considered. Obstacles are considered in four categories, namely target selection, trafficking of CAR-engineered cells to tumour deposits, the need to overcome the physical, chemical and biological hurdles to immune effector function that operate within the tumour microenvironment and selection of the best host cells for CAR engineering. A range of pre-clinical technologies that have been developed in an effort to overcome these issues are also surveyed. Although clinical progress comes dropping slow, rapid and continued advances in cellular engineering and manufacture, coupled with the emergence of several complementary interventions bodes well for the future success of CAR T-cell immunotherapy of solid tumours.
UR - http://www.scopus.com/inward/record.url?scp=85164294921&partnerID=8YFLogxK
U2 - 10.1002/ctd2.179
DO - 10.1002/ctd2.179
M3 - Review article
VL - 3
JO - Clinical and Translational Discovery
JF - Clinical and Translational Discovery
IS - 2
M1 - e179
ER -