4.6 Review

Directing CAR T cells towards the tumor vasculature for the treatment of solid tumors

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出版社

ELSEVIER
DOI: 10.1016/j.bbcan.2022.188701

关键词

Cancer; CAR T cell; Immune suppression; Tumor microenvironment; Angiogenesis

资金

  1. Dutch Cancer Society [KWF 2018-11651]
  2. EU, MSCA-IF-2019, AngioCAR
  3. EU, FP7-PEOPLE-2012-IEF, GENE [328695]
  4. [KWF 2020-13009]

向作者/读者索取更多资源

In this review, recent advances in CAR T cell therapy against solid tumors, with a focus on targeting the tumor vasculature, are discussed. Opportunities to overcome challenges and barriers through engineering of CAR T cells to enhance trafficking, safety, and efficacy are also explored.
For successful application of chimeric antigen receptor (CAR) T cell therapy in solid tumors, major hurdles have to be overcome. CAR T cells have to cross the vascular barrier, which is hampered by the anergic state of the tumor vasculature, characterized by suppressed levels of leukocyte adhesion molecules on the endothelium. Additional immunosuppressive mechanisms in the solid tumor microenvironment can affect infiltration, activity and persistence of CAR T cells. Redirecting CAR T cells towards the tumor vasculature poses a possible solution, as molecular targets of tumor endothelial cells can be directly engaged from within the blood.In this review, we discuss recent advances in CAR T cell therapy against solid tumors, with a focus on targeting the tumor vasculature. Furthermore, we discuss opportunities to overcome challenges and barriers through engineering of CAR T cells to enhance trafficking, safety and efficacy.

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