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A novel TREM1/DAP12-based multiple chain CAR-T cell targets PTK7 in ovarian cancer therapy

Tongpeng Xu1, Chen Wang2, Xiaoyan Wang3

  • 1Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.

Medical Oncology (Northwood, London, England)
|July 5, 2023
PubMed

Insights

Novel chimeric antigen receptor T (CAR-T) cells targeting PTK7 show promise for ovarian cancer treatment. These engineered CAR-T cells effectively eliminated ovarian tumors in preclinical studies, offering a potential new therapy.

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Chimeric antigen receptor T (CAR-T) cell therapy is effective against blood cancers but limited for solid tumors like ovarian cancer.
  • Ovarian cancer remains a significant challenge, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To develop and assess the efficacy of novel CAR-T cells targeting PTK7 (a protein overexpressed in ovarian cancer) via TREM1/DAP12 signaling.
  • To evaluate the anti-tumor potential of these engineered T cells against ovarian cancer.

Main Methods:

  • Immunohistochemical staining and flow cytometry were used to confirm PTK7 expression in ovarian cancer tissues and cells.
  • In vitro assays (real-time cell analysis, ELISA) and in vivo xenograft models were employed to evaluate the anti-tumor effects of PTK7-targeting CAR-T cells.

Main Results:

  • PTK7 was significantly expressed in ovarian cancer tissues and cells.
  • PTK7-targeting CAR-T cells demonstrated potent in vitro cytotoxicity against PTK7-positive ovarian cancer cells.
  • These CAR-T cells effectively eradicated tumors in a preclinical in vivo model.

Conclusions:

  • TREM1/DAP12-based PTK7 CAR-T cells exhibit significant anti-tumor activity against ovarian cancer.
  • This novel CAR-T cell strategy holds potential for treating ovarian cancer, warranting further clinical investigation.
Keywords:
CAR-T cellDAP12Ovarian cancerPTK7TREM1

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