TY - JOUR
T1 - The emerging role for CAR T cells in solid tumor oncology
AU - Klobuch, Sebastian
AU - Seijkens, Tom T. P.
AU - Haanen, John B. A. G.
N1 - Funding Information: ICMJE uniform disclosure form (available at https://cco. amegroups.com/article/view/10.21037/cco-22-125/coif). SK participated on an advisory board for Regeneron. JBAGH provided advise to AZ, BMS, CureVac, GSK, Imcyse, Iovance Bio, Instil Bio, Immunocore, Ipsen, Merck Serono, MSD, Molecular Partners, Novartis, Pfizer, Roche/ Genentech, Sanofi, Scenic, TRV. JBAGH is member of scientific advisory boards for Achilles Tx, BioNTech US, Instil Bio, PokeAcell, T-Knife, Scenic and Neogene Therapeutics. JBAGH received grant support from Amgen, Asher Bio, BioNTech, BMS, Novartis, Sastra. The other author has no conflicts of interest to declare. Publisher Copyright: © Chinese Clinical Oncology. All rights reserved.
PY - 2023/4/1
Y1 - 2023/4/1
N2 - In recent years, treatment with chimeric antigen receptor (CAR) T-cells has revolutionized the outcomes of patients with relapsed or refractory hematological malignancies with long-term remissions in >30% of patients. Similarly, the introduction of immune checkpoint inhibitor therapy changed the therapeutic landscape for several solid malignancies also leading to impressive long-term remission in patients. However, so far CAR T-cell therapy in solid tumors has shown low response rates and especially a lack of long-term remissions. This review focuses on the latest clinical advances and discusses promising results seen with CAR T-cells exploring new target antigens. We then review relevant challenges limiting long-term responses with CAR T-cell therapy in solid tumors like CAR T-cell persistence and target antigen expression. In addition, there is an increasing understanding on T-cell function and dysfunction within the immunosuppressive tumor microenvironment. This comprises of inhibitory cytokines and checkpoint molecules limiting the killing capacity of CAR T-cells. Finally, we will discuss how this deeper knowledge can be used to develop CAR T-cell therapies overcoming these inhibitory factors and results in CAR T-cell products with higher efficacy and safety. These technological developments will hopefully lead to enhanced clinical activity and improved solid tumor patient outcomes in the near future.
AB - In recent years, treatment with chimeric antigen receptor (CAR) T-cells has revolutionized the outcomes of patients with relapsed or refractory hematological malignancies with long-term remissions in >30% of patients. Similarly, the introduction of immune checkpoint inhibitor therapy changed the therapeutic landscape for several solid malignancies also leading to impressive long-term remission in patients. However, so far CAR T-cell therapy in solid tumors has shown low response rates and especially a lack of long-term remissions. This review focuses on the latest clinical advances and discusses promising results seen with CAR T-cells exploring new target antigens. We then review relevant challenges limiting long-term responses with CAR T-cell therapy in solid tumors like CAR T-cell persistence and target antigen expression. In addition, there is an increasing understanding on T-cell function and dysfunction within the immunosuppressive tumor microenvironment. This comprises of inhibitory cytokines and checkpoint molecules limiting the killing capacity of CAR T-cells. Finally, we will discuss how this deeper knowledge can be used to develop CAR T-cell therapies overcoming these inhibitory factors and results in CAR T-cell products with higher efficacy and safety. These technological developments will hopefully lead to enhanced clinical activity and improved solid tumor patient outcomes in the near future.
KW - Chimeric antigen receptor T-cells (CAR T-cells)
KW - adoptive T-cell therapy
KW - solid tumors
UR - http://www.scopus.com/inward/record.url?scp=85159727673&partnerID=8YFLogxK
U2 - https://doi.org/10.21037/cco-22-125
DO - https://doi.org/10.21037/cco-22-125
M3 - Review article
C2 - 37160670
SN - 2304-3865
VL - 12
SP - 19
JO - Chinese clinical oncology
JF - Chinese clinical oncology
IS - 2
M1 - 19
ER -