CXCR2‐modified CAR‐T cells have enhanced trafficking ability that improves treatment of hepatocellular carcinoma

Unlike hematological malignancies, solid tumors have proved to be less susceptible to chimeric antigen receptor (CAR)‐T cell therapy, which is partially caused by reduced accumulation of therapeutic T cells in tumor site. Since efficient trafficking is the precondition and pivotal step for infused CAR‐T cells to exhibit their anti‐tumor function, strategies are highly needed to improve the trafficking ability of CAR‐T cells for solid tumor treatment. Here, based on natural lymphocyte chemotaxis theory and characteristics of solid tumor microenvironments, we explored the possibility of enhancing CAR‐T cell trafficking by using chemokine receptors. Our study found that compared with other chemokines, several CXCR2 ligands showed relatively high expression level in human hepatocellular carcinoma tumor tissues and cell lines. However, both human peripheral T cells and hepatocellular carcinoma tumor infiltrating T cells lacked expression of CXCR2. CXCR2‐expressing CAR‐T cells exhibited identical cytotoxicity but displayed significantly increased migration ability in vitro. In a xenograft tumor model, we found that expressing CXCR2 in CAR‐T cells could significantly accelerate in vivo trafficking and tumor‐specific accumulation, and improve anti‐tumor effect of these cells.

• Publication year

  2020

• Venue

  European Journal of Immunology

• Publication date

  2020-01-24

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1002/eji.201948457PMID 31981231
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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