CD27 enhances the killing effect of CAR T cells targeting trophoblast cell surface antigen 2 in the treatment of solid tumors
- 30 June 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cancer Immunology, Immunotherapy
- Vol. 70 (7), 2059-2071
- https://doi.org/10.1007/s00262-020-02838-8
Abstract
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-7R alpha 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.Funding Information
- Guangdong Science and Technology Department (2017A050501010, 2016A050503023)
- Guangzhou Science, Technology and Innovation Commission (201807010042)
This publication has 54 references indexed in Scilit:
- TROP2 Expressed in the Trunk of the Ureteric Duct Regulates Branching Morphogenesis during Kidney DevelopmentPLOS ONE, 2011
- The Pim Kinase Pathway Contributes to Survival Signaling in Primed CD8+ T Cells upon CD27 CostimulationThe Journal of Immunology, 2010
- Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19Blood, 2010
- Control of Established Melanoma by CD27 Stimulation Is Associated With Enhanced Effector Function and Persistence, and Reduced PD-1 Expression of Tumor Infiltrating CD8+ T CellsJournal of Immunotherapy, 2010
- Trop-2 overexpression as an independent marker for poor overall survival in ovarian carcinoma patientsEuropean Journal of Cancer, 2010
- Trop2: A possible therapeutic target for late stage epithelial carcinomasBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2009
- Potential hepatic stem cells reside in EpCAM+ cells of normal and injured mouse liverDevelopment, 2009
- The role of TNF superfamily members in T-cell function and diseasesNature Reviews Immunology, 2009
- Identification of Trop-2 as an oncogene and an attractive therapeutic target in colon cancersMolecular Cancer Therapeutics, 2008
- CD28-mediated co-stimulation: a quantitative support for TCR signallingNature Reviews Immunology, 2003