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Development of NKG2D-based chimeric antigen receptor-T cells for gastric cancer treatment

Kelong Tao1, Meng He2, Feng Tao1

  • 1Department of Gastrointestinal Surgery, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), No. 568 Zhongxing North Road, Shaoxing, 312000, Zhejiang, People's Republic of China.

Cancer Chemotherapy and Pharmacology
|August 23, 2018
PubMed

Insights

Novel chimeric antigen receptor (CAR) T-cell therapy targeting NKG2D ligands shows potent anti-gastric cancer activity. This NKG2D-CAR-T therapy suppressed tumor growth in vivo and may offer new treatment options for advanced gastric cancer.

Area of Science:

  • Immunotherapy
  • Oncology
  • Cellular Therapy

Background:

  • Gastric cancer is a leading cause of cancer mortality with limited treatment options for advanced stages.
  • Chimeric antigen receptor (CAR) T-cell therapy has shown success in blood cancers and is being explored for solid tumors.
  • NKG2D ligands are broadly expressed on gastric cancer cells, indicating potential therapeutic targets.

Purpose of the Study:

  • To evaluate the efficacy of NKG2D-based CAR T-cells against gastric cancer.
  • To investigate the combination of NKG2D-CAR-T therapy with chemotherapy.

Main Methods:

  • Engineering T-cells with a second-generation NKG2D-based CAR (NKG2D-CAR-T cells).
  • Assessing in vitro cytolytic activity of NKG2D-CAR-T cells against gastric cancer cell lines.
  • Evaluating in vivo anti-tumor efficacy in gastric cancer xenograft models.
  • Investigating the effect of cisplatin on NKG2D ligand expression and CAR-T cell susceptibility.

Main Results:

  • NKG2D-CAR-T cells exhibited significantly enhanced cytolytic activity against gastric cancer cells compared to control T-cells.
  • NKG2D-CAR-T cells significantly suppressed the growth of established gastric cancer xenografts in vivo.
  • Cisplatin treatment upregulated NKG2D ligand expression on gastric cancer cells, increasing their susceptibility to NKG2D-CAR-T cell-mediated killing.

Conclusions:

  • NKG2D-based CAR-T cells demonstrate potent in vitro and in vivo anti-tumor activity against gastric cancer.
  • This therapy holds promise as a novel treatment strategy for gastric cancer, potentially in combination with chemotherapy.
Keywords:
Chimeric antigen receptorGastric cancerNKG2D

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