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The Role of Immune Checkpoints after Cellular Therapy

Department of Hematology, Oncology and Rheumatology, University Hospital Bonn, 53127 Bonn, Germany
UKIM 5, Hematology and Oncology, Medical University Innsbruck, 6020 Innsbruck, Austria
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(10), 3650;
Received: 27 April 2020 / Revised: 18 May 2020 / Accepted: 18 May 2020 / Published: 21 May 2020
Cellular therapies utilize the powerful force of the human immune system to target malignant cells. Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the most established cellular therapy, but chimeric antigen receptor (CAR) T cell therapies have gained attention in recent years. While in allo-HCT an entirely novel allogeneic immune system facilitates a so-called Graft-versus-tumor, respectively, Graft-versus-leukemia (GvT/GvL) effect against high-risk hematologic malignancies, in CAR T cell therapies genetically modified autologous T cells specifically attack target molecules on malignant cells. These therapies have achieved high success rates, offering potential cures in otherwise detrimental diseases. However, relapse after cellular therapy remains a serious clinical obstacle. Checkpoint Inhibition (CI), which was recently designated as breakthrough in cancer treatment and consequently awarded with the Nobel prize in 2018, is a different way to increase anti-tumor immunity. Here, inhibitory immune checkpoints are blocked on immune cells in order to restore the immunological force against malignant diseases. Disease relapse after CAR T cell therapy or allo-HCT has been linked to up-regulation of immune checkpoints that render cancer cells resistant to the cell-mediated anti-cancer immune effects. Thus, enhancing immune cell function after cellular therapies using CI is an important treatment option that might re-activate the anti-cancer effect upon cell therapy. In this review, we will summarize current data on this topic with the focus on immune checkpoints after cellular therapy for malignant diseases and balance efficacy versus potential side effects. View Full-Text
Keywords: cellular therapy; allogeneic stem cell transplantation; CAR T cell therapy; immune checkpoints; checkpoint inhibition; GvL; GvHD cellular therapy; allogeneic stem cell transplantation; CAR T cell therapy; immune checkpoints; checkpoint inhibition; GvL; GvHD
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Schmitz, F.; Wolf, D.; Holderried, T.A. The Role of Immune Checkpoints after Cellular Therapy. Int. J. Mol. Sci. 2020, 21, 3650.

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