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Year : 2017  |  Volume : 3  |  Issue : 4  |  Page : 139-145

Combination of Interleukin-11Rα chimeric antigen receptor T-cells and programmed death-1 blockade as an approach to targeting osteosarcoma cells In vitro

Department of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

Correspondence Address:
Hatel Rana Moonat
Texas Children's Cancer and Hematology Centers, Texas Children's Hospital The Woodlands, 17580 I-45 S, Suite 450, The Woodlands, TX 77384
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ctm.ctm_3_17

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Aim: To test whether combining interleukin (IL)-11Rα chimeric antigen receptor (CAR) T-cells with an anti-programmed death (PD-1) antibody (an immune checkpoint inhibitor) is an effective therapeutic approach in osteosarcoma (OS), allowing improved tumor eradication. Methods: IL-11Rα-CAR T-cells were cocultured in vitro with human LM7 OS tumor cells (with and without anti-PD-1 antibody). Coculture of LM7 cells with purified T-cells served as the control. Cytotoxicity and surface PD-1 expression were analyzed in all groups. Results: PD-1 expression increased during expansion of CAR T-cells. Exposure of immune cells to tumor cells in vitro subsequently decreased surface PD-1 expression on the CAR T-cells. Addition of an anti-PD-1 antibody (Clone J110) to further decrease surface PD-1 expression on CAR T-cells before coculture did not enhance cytotoxic effects of the CAR T-cells against LM7 cells. Conclusion: This combination of IL-11Rα-CAR T-cells and an anti-PD-1 antibody did not provide any additional cytotoxic benefit over IL-11Rα-CAR T-cell therapy alone in this setting. Further studies are needed as simple interference with surface PD-1 expression alone may not be sufficient to inhibit this immune checkpoint pathway to then enhance IL-11Rα-CAR T-cell therapeutic effects.

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