Targeting endothelial cell anergy to improve CAR T cell therapy for solid tumors.
Biochim Biophys Acta Rev Cancer
; 1879(5): 189155, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-39019408
ABSTRACT
Chimeric antigen receptor (CAR) T cell therapy presents significant results, especially for the treatment of hematologic malignancies. However, there are limitations and challenges to be overcome to achieve similar success for the treatment of solid tumors. These challenges involve selection of the target, infiltration into the tumor microenvironment and maintenance of functionality. The tumor vasculature is a major barrier for leukocytes to enter the tumor parenchyma. Due to the exposure of the vasculature to angiogenic growth factors during tumor progression, the endothelial cells become anergic to inflammatory cytokines, resulting in reduced leukocyte adhesion molecule expression. As such adhesion molecules are a prerequisite for leukocyte extravasation, endothelial cell anergy allows tumors to escape from endogenous immunity, as well as from cellular immunotherapies such as CAR T cells. Hence, overcoming endothelial cell anergy, e.g. through the administration of angiogenesis inhibitors, is believed to restore anti-tumor immunity. Concomitantly, both endogenous immune cells as well as cellular therapeutics such as CAR T cells can permeate into the tumor parenchyma. Here, we discuss how prior or concomitant treatment with an antiangiogenic drug can improve CAR T cell therapy, to become an attractive strategy for the treatment of solid tumors.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Immunotherapy, Adoptive
/
Clonal Anergy
/
Endothelial Cells
/
Tumor Microenvironment
/
Receptors, Chimeric Antigen
/
Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Biochim Biophys Acta Rev Cancer
Year:
2024
Document type:
Article
Affiliation country:
Países Bajos
Country of publication:
Países Bajos