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Extracorporeal photopheresis as a promising strategy for the treatment of graft-versus-host disease after CAR T-cell therapy

Graft-versus-host disease (GVHD) occurs in about 10% to 33% of patients receiving “allogeneic” or “autologous” chimeric antigen receptor T (CAR-T) cells after preceding allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to the substantial presence of alloreactive T cells. Extracorpor...

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Main Authors: Han, Huixiu (Author) , Wang, Lei (Author) , Ding, Yuntian (Author) , Neuber, Brigitte (Author) , Hückelhoven-Krauss, Angela (Author) , Lin, Min (Author) , Yao, Hao (Author) , Chen, Qian (Author) , Sauer, Tim (Author) , Schubert, Maria-Luisa (Author) , Guo, Zhiqiang (Author) , Müller-Tidow, Carsten (Author) , Schmitt, Michael (Author) , Schmitt, Anita (Author)
Format: Article (Journal)
Language:English
Published: June 11 2024
In: Blood advances
Year: 2024, Volume: 8, Issue: 11, Pages: 2675-2690
ISSN:2473-9537
DOI:10.1182/bloodadvances.2023012463
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/bloodadvances.2023012463
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Author Notes:Huixiu Han, Lei Wang, Yuntian Ding, Brigitte Neuber, Angela Hückelhoven-Krauss, Min Lin, Hao Yao, Qian Chen, Tim Sauer, Maria-Luisa Schubert, Zhiqiang Guo, Carsten Müller-Tidow, Michael Schmitt, and Anita Schmitt
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Summary:Graft-versus-host disease (GVHD) occurs in about 10% to 33% of patients receiving “allogeneic” or “autologous” chimeric antigen receptor T (CAR-T) cells after preceding allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to the substantial presence of alloreactive T cells. Extracorporeal photopheresis (ECP) shows promising clinical outcomes in the treatment of GVHD after allo-HSCT without hampering antitumor and antiviral effects. This raises an interesting question: whether ECP might constitute a new way to treat patients with GVHD after CAR T-cell therapy without compromising CAR-T cells significantly. Third-generation CD19-specific CAR-T cells were generated and an in vitro ECP protocol was established. The impact of ECP on CAR-T cells was comprehensively investigated in 2 models: the nondilution model reflects days after CAR T-cell infusion and the dilution model weeks after infusion. The therapeutic effect of ECP on GVHD was examined in an in vitro mixed lymphocyte reaction (MLR) assay. We found, ECP-treated CAR-T cells demonstrated reduced potency in inducing alloreaction compared with that of the group without ECP treatment in MLR assay. ECP could selectively induce apoptosis, thereby enriching the naive and central memory CAR-T cells with a reduced alloreactivity. The cytokine milieu of CAR-T cells could be switched from immune stimulation to immune tolerance in both models. Moreover, ECP could modulate the proliferative capacity of CAR-T cells without hampering their long-term functionality in the dilution model. In conclusion, ECP constitutes a promising treatment strategy for GVHD after allo-HSCT and CAR T-cell transfusion, as ECP reduces the alloreactivity without hampering CAR T-cell functionality.
Item Description:Online veröffentlicht: 30. Mai 2024
Gesehen am 20.11.2024
Physical Description:Online Resource
ISSN:2473-9537
DOI:10.1182/bloodadvances.2023012463

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