Anti-CD166/4-1BB chimeric antigen receptor T cell therapy for the treatment of osteosarcoma

Yitian Wang1,2, Wei Yu1,2, Jian Zhu1,2

  • 1Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009, Zhejiang, People's Republic of China.

Abstract

Insights

Chimeric antigen receptor (CAR)-T cells targeting CD166 show promise for osteosarcoma treatment. These engineered T cells effectively killed osteosarcoma cells in vitro and in vivo, suggesting a potential new therapy.

Area of Science:

  • Immunotherapy
  • Oncology
  • Cellular Therapy

Background:

  • Chimeric antigen receptor (CAR)-T cell therapy is highly effective against blood cancers.
  • Its application against solid tumors, like osteosarcoma, remains challenging.

Purpose of the Study:

  • To investigate CD166 as a potential target for CAR-T cell therapy in osteosarcoma.
  • To evaluate the efficacy and safety of CD166-specific CAR-T cells against osteosarcoma.

Main Methods:

  • Human osteosarcoma cell lines were analyzed for CD166 expression.
  • CD166-specific CAR-T cells (CD166.BBζ) were generated via viral gene transfer and expanded.
  • In vitro and in vivo assays assessed the cytotoxic activity of CD166.BBζ CAR-T cells against osteosarcoma.

Main Results:

  • CD166 was selectively expressed on human osteosarcoma cell lines.
  • CD166.BBζ CAR-T cells demonstrated potent killing of osteosarcoma cells in vitro, proportional to CD166 expression.
  • In vivo studies showed tumor regression and no significant toxicity following CD166.BBζ CAR-T cell administration in mice.

Conclusions:

  • CD166.BBζ CAR-T cells represent a potential novel therapeutic strategy for osteosarcoma.
  • Targeting CD166 with CAR-T cells offers a promising avenue for future clinical applications in osteosarcoma treatment.

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