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The killing effect of novel bi-specific Trop2/PD-L1 CAR-T cell targeted gastric cancer

Wei Zhao1,2, Lizhou Jia3,2,4, Mingjiong Zhang2

  • 1Department of Pathology, Nanjing First Hospital, Nanjing Medical University Nanjing 210006, China.

American Journal of Cancer Research
|September 10, 2019
PubMed

Insights

This study developed novel bi-specific Trop2/PD-L1 CAR-T cells to improve solid tumor treatment. These enhanced CAR-T cells demonstrated superior efficacy against gastric cancer both in vitro and in vivo.

Area of Science:

  • Immunotherapy
  • Oncology
  • Biotechnology

Background:

  • Solid tumor treatment with CAR-T cell technology faces limitations due to tumor heterogeneity and complex microenvironments.
  • Targeting multiple tumor antigens and immune checkpoints simultaneously is crucial for enhancing CAR-T cell efficacy.

Purpose of the Study:

  • To develop and evaluate bi-specific Trop2/PD-L1 CAR-T cells for improved gastric cancer treatment.
  • To assess the in vitro and in vivo anti-tumor activity of these novel CAR-T cells compared to mono-specific CAR-T cells.

Main Methods:

  • Lentiviral infection was used to generate third-generation bi-specific Trop2/PD-L1 CAR-T cells.
  • In vitro studies utilized CCK-8 and ELASA assays to confirm specific killing ability and cytokine production (IFN-γ, IL-2).
  • In vivo efficacy was evaluated using a human gastric tumor xenograft model with intratumoral injection.

Main Results:

  • Bi-specific Trop2/PD-L1 CAR-T cells exhibited significantly higher killing ability against gastric cancer cells than mono-specific CAR-T cells and controls.
  • Elevated production of IFN-γ and IL-2 was observed in response to Trop2 and PD-L1 overexpression.
  • Intratumoral injection of bi-specific CAR-T cells significantly reduced tumor growth in vivo, outperforming mono-specific CAR-T cells.

Conclusions:

  • Bi-specific Trop2/PD-L1 CAR-T cells effectively target Trop2, PD-L1, and checkpoint blockade in gastric cancer.
  • This novel CAR-T cell strategy shows promise for enhancing the therapeutic efficacy of CAR-T cells in solid tumors.
Keywords:
Gastric cancerPD-L1Trop2chimeric antigen receptorsimmune microenvironment

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