Science China Life Sciences

, Volume 59, Issue 4, pp 386–397 | Cite as

Phase 1 clinical trial demonstrated that MUC1 positive metastatic seminal vesicle cancer can be effectively eradicated by modified Anti-MUC1 chimeric antigen receptor transduced T cells

  • Fengtao You
  • Licui Jiang
  • Bozhen Zhang
  • Qiang Lu
  • Qiao Zhou
  • Xiaoyang Liao
  • Hong Wu
  • Kaiqi Du
  • Youcai Zhu
  • Huimin Meng
  • Zhishu Gong
  • Yunhui Zong
  • Lei Huang
  • Man Lu
  • Jirong Tang
  • Yafen Li
  • Xiaochen Zhai
  • Xiangling Wang
  • Sisi Ye
  • Dan Chen
  • Lei Yuan
  • Lin Qi
  • Lin Yang
Open Access
Research Paper SPECIAL TOPIC: Fighting cancer with armed T cells

Abstract

Recent progress in chimeric antigen receptor-modified T-cell (CAR-T cell) technology in cancer therapy is extremely promising, especially in the treatment of patients with B-cell acute lymphoblastic leukemia. In contrast, due to the hostile immunosuppressive microenvironment of a solid tumor, CAR T-cell accessibility and survival continue to pose a considerable challenge, which leads to their limited therapeutic efficacy. In this study, we constructed two anti-MUC1 CAR-T cell lines. One set of CAR-T cells contained SM3 single chain variable fragment (scFv) sequence specifically targeting the MUC1 antigen and co-expressing interleukin (IL) 12 (named SM3-CAR). The other CAR-T cell line carried the SM3 scFv sequence modified to improve its binding to MUC1 antigen (named pSM3-CAR) but did not co-express IL-12. When those two types of CAR-T cells were injected intratumorally into two independent metastatic lesions of the same MUC1+ seminal vesicle cancer patient as part of an interventional treatment strategy, the initial results indicated no side-effects of the MUC1 targeting CAR-T cell approach, and patient serum cytokines responses were positive. Further evaluation showed that pSM3-CAR effectively caused tumor necrosis, providing new options for improved CAR-T therapy in solid tumors.

Keywords

MUC1 CAR-T therapy solid tumor seminal vesicle cancer 

Supplementary material

11427_2016_5024_MOESM1_ESM.pptx (537 kb)
Supplementary material, approximately 538 KB.

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Copyright information

© The Author(s) 2016

Authors and Affiliations

  • Fengtao You
    • 1
    • 2
    • 3
  • Licui Jiang
    • 2
    • 3
  • Bozhen Zhang
    • 2
    • 3
  • Qiang Lu
    • 4
  • Qiao Zhou
    • 4
  • Xiaoyang Liao
    • 4
  • Hong Wu
    • 4
  • Kaiqi Du
    • 5
  • Youcai Zhu
    • 5
  • Huimin Meng
    • 1
  • Zhishu Gong
    • 6
  • Yunhui Zong
    • 2
    • 3
  • Lei Huang
    • 2
    • 3
  • Man Lu
    • 2
    • 3
  • Jirong Tang
    • 2
    • 3
  • Yafen Li
    • 2
    • 3
  • Xiaochen Zhai
    • 7
  • Xiangling Wang
    • 7
  • Sisi Ye
    • 2
    • 3
  • Dan Chen
    • 2
    • 3
  • Lei Yuan
    • 8
  • Lin Qi
    • 2
    • 3
  • Lin Yang
    • 1
    • 2
    • 3
    • 7
  1. 1.The Cyrus Tang Hematology Center; Collaborative Innovation Center of HematologySoochow UniversitySuzhouChina
  2. 2.Suzhou Cancer Immunotherapy and Diagnosis Engineering CenterSuzhouChina
  3. 3.Persongen Biomedicine (Suzhou) Co., LtdSuzhouChina
  4. 4.West China Hospital, Sichuan UniversityChengduChina
  5. 5.Department of Cardiothoracic SurgeryChinese People’s Armed Police Force of Zhejiang Corps HospitalJiaxingChina
  6. 6.The Medical Group of Zhengzhou First People’s HospitalZhengzhouChina
  7. 7.College of PharmacyXi’an Jiaotong UniversitySuzhouChina
  8. 8.Department of HematologyChinese PLA General HospitalBeijingChina

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