Targeting endothelial cell anergy to improve CAR T cell therapy for solid tumors.

Autor: Wachholz GE; Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam, the Netherlands., Akbari P; Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam, the Netherlands., Huijbers EJM; Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam, the Netherlands., Jalan P; Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam, the Netherlands., van Beijnum JR; Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam, the Netherlands., Griffioen AW; Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam, the Netherlands. Electronic address: a.griffioen@amsterdamumc.nl.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Reviews on cancer [Biochim Biophys Acta Rev Cancer] 2024 Sep; Vol. 1879 (5), pp. 189155. Date of Electronic Publication: 2024 Jul 15.
DOI: 10.1016/j.bbcan.2024.189155
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Arjan Griffioen reports financial support was provided by Amsterdam UMC Location VUmc. Arjan Griffioen reports financial support was provided by European Union. Arjan Griffioen reports financial support was provided by Dutch Cancer Society. Elisabeth J. M. Huijbers reports financial support was provided by European Union. Parvin Akbari reports financial support was provided by European Union. Arjan Griffioen reports financial support was provided by Netherlands Foundation of Scientific Research Institutes. Judy R. van Beijnum reports financial support was provided by Cancer Center Amsterdam (CCA). Arjan Griffioen reports a relationship with CimCure B.V. that includes: board membership. Gabriela Elis Wachholz reports a relationship with CimCure B.V. that includes: employment. Elisabeth Huijbers reports a relationship with CimCure B.V. that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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