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CD27 enhances the killing effect of CAR T cells targeting trophoblast cell surface antigen 2 in the treatment of solid tumors.
Chen, Huanpeng; Wei, Fengjiao; Yin, Meng; Zhao, Qingyu; Liu, Zhonghua; Yu, Bolan; Huang, Zhaofeng.
Affiliation
  • Chen H; Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, N1311 Rm, No. 10 Bld, 74 Zhongshan 2nd Rd, Guangzhou, 510080, China.
  • Wei F; Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, China.
  • Yin M; Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, N1311 Rm, No. 10 Bld, 74 Zhongshan 2nd Rd, Guangzhou, 510080, China.
  • Zhao Q; Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, China.
  • Liu Z; Sun Yat-Sen University Cancer Center, Guangzhou, China.
  • Yu B; Sun Yat-Sen University Cancer Center, Guangzhou, China.
  • Huang Z; Laboratory Animal Center, South China Agricultural University, Guangzhou, China.
Cancer Immunol Immunother ; 70(7): 2059-2071, 2021 Jul.
Article in En | MEDLINE | ID: mdl-33439295
Chimeric antigen receptor (CAR) T cell therapy, a type of adoptive cell therapy, has been successfully used when treating lymphoma malignancies, but not nearly as successful in treating solid tumors. Trophoblast cell surface antigen 2 (Trop2) is expressed in various solid tumors and plays a role in tumor growth, invasion, and metastasis. In this study, a CAR targeting Trop2 (T2-CAR) was developed with different co-stimulatory intercellular domains. T2-CAR T cells demonstrated a powerful killing ability in the presence of Trop2-positive cells following an in vitro assay. Moreover, T2-CAR T cells produced multiple effector cytokines under antigen stimulation. In tumor-bearing mouse models, the CD27-based T2-CAR T cells showed a higher antitumor activity. Additionally, more CD27-based T2-CAR T cells survived in tumor-bearing mice spleens as well as in the tumor tissue. CD27-based T2-CAR T cells were also found to upregulate IL-7Rα expression, while downregulating PD-1 expression. In conclusion, the CD27 intercellular domain can enhance the T2-CAR T cell killing effect via multiple mechanisms, thus indicating that a CD27-based T2-CAR T cell approach is suitable for clinical applications.
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Full text: 1 Database: MEDLINE Main subject: Breast Neoplasms / Cell Adhesion Molecules / Immunotherapy, Adoptive / Tumor Necrosis Factor Receptor Superfamily, Member 7 / Receptors, Chimeric Antigen Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Year: 2021 Type: Article

Full text: 1 Database: MEDLINE Main subject: Breast Neoplasms / Cell Adhesion Molecules / Immunotherapy, Adoptive / Tumor Necrosis Factor Receptor Superfamily, Member 7 / Receptors, Chimeric Antigen Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Year: 2021 Type: Article