4.4 Article

Overexpressed CXCR4 and CCR7 on the surface of NK92 cell have improved migration and anti-tumor activity in human colon tumor model

Journal

ANTI-CANCER DRUGS
Volume 31, Issue 4, Pages 333-344

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CAD.0000000000000868

Keywords

adoptive tumor immunotherapy; CCR7; chemokine receptor; CXCR4; NK92

Funding

  1. major science and technology project of Zhejiang Province, China [4125C4011724448]
  2. national natural science foundation of China [81072495]

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Successive infusion of natural killer cells is increasingly being explored as a treatment for cancer patients. The inadequate homing of natural killer cells into the tumor site resulted in the poor efficacy of natural killer cells on solid tumors. For the adoptive transfer of tumor-directed natural killer cell has been proved effective, it is hypothesized that there must be more association between the tumor-produced chemokines and the natural killer cells-expressed chemokine receptors. Increased CXCL12 and CCL21 could ameliorated colorectal cancer via generating an anti-tumor environment by preferentially attracting natural killer cells which expressed the chemokine receptor CXCR4 and CCR7. This study demonstrated that overexpressed CXCR4 and CCR7 on the surface of NK92 cell enhanced their migration to human colon cells. Moreover, the administration of such natural killer cells resulted in tumor shrinkage and a significantly increased survival of experimental mice when compared to ones undergoing the treatment of xenografts with natural killer cells expressing only the mock control. These suggested that chemokine receptor engineered natural killer cells could be a promising tool to improve adoptive tumor immunotherapy.

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