Basing on uPAR-binding fragment to design chimeric antigen receptors triggers antitumor efficacy against uPAR expressing ovarian cancer cells - 31/07/19
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Graphical abstract |
Highlights |
• | This study first reports uPAR as a candidate target for CAR T cell therapy. |
• | To recognize uPAR on cancer cells, do not incorporate scFv but a natural binding ligand, ATF as the extracellular domain of CARs. |
• | ATF-CAR T cells can lyse uPAR-positive ovarian cancer cells with a satisfactory efficacy. |
• | Considering that uPAR expression is not only specific to tumor cells but also to stromal cells in tumors, anti-uPAR CAR T cell therapy shows promise for further studies and trials. |
Abstract |
Due to the success of chimeric antigen receptors (CARs) in hematological tumors, CARs are also being studied to treat solid tumors. Improving the ability of CARs to penetrate solid tumor tissues is one of the biggest challenges. As the most malignant cancer of the female reproductive system, the survival rate of ovarian cancer has not been significantly improved by traditional therapy methods; therefore, it is necessary to develop new therapeutic targets and new immunotherapy methods for ovarian cancer. UPAR is a glysocylphosphatidylinositol (GPI) anchoring membrane protein that is differentially expressed in normal tissues and ovarian cancer tissues. It has been shown that uPAR up-regulation promotes tumor development, proliferation, invasion, and metastasis, and uPAR is also up-regulated in tumor matrix components. In our study, CARs were designed using the natural ligand binding fragment of uPAR for ovarian cancer.
Le texte complet de cet article est disponible en PDF.Keywords : UPAR, Ovarian cancer, Chimeric antigen receptor, Effector to target ratio, Cytokines, Granzyme B
Plan
Vol 117
Article 109173- septembre 2019 Retour au numéro
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