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•ECP constitutes a promising therapeutic approach for GVHD after CAR T-cell infusion.•ECP reduces alloreactivity without compromising the functionality of CAR-T cells.

In previous work, the authors demonstrated that kidney transplant recipients developed donor-specific unresponsiveness when they were given a pretransplant infusion of modified donor-derived PBMCs. In this study, they provide evidence that the immunosuppressive properties of these cells persist and the donor-specific unresponsiveness is long-lasting. In the four patients who received the highest dose of the modified immune cells, administration of these cells was associated with a striking increase in IL-10–producing regulatory B lymphocytes and evidence of the consensus gene expression signature of operational tolerance. In vitro, donor-specific unresponsiveness was abolished after B lymphocyte depletion, suggesting a direct pathophysiologic role for regulatory B lymphocytes. These findings support the notion that modified donor-derived PBMCs may be useful in kidney transplantation, but this approach requires further validation and rigorous controlled randomized studies.

In patients with steroid-refractory/resistant graft-versus-host disease (GvHD), extracorporeal photopheresis (ECP) has been identified as a promising therapeutic strategy due to its safety profile and convincing clinical response rates.

Introduction

Introduction:After approval of CD19.CAR-T cell therapy by both FDA and EMA, chimeric antigen receptor T (CAR-T) cell therapy has been established as a new and innovative therapy method for patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). Because of this, there is great need for reliable methods for CAR-T cell monitoring by clinicians to further assess cell expansion, distribution and persistence in patients. This is both necessary for CAR-T cell manufacturing sites and researchers to assess transduction efficiency and vector copy numbers per cell. Therefore, we analyzed CAR expression of CD19.CAR-T cells using flow cytometry as well as quantitative polymerase chain reaction (qPCR).

Schubert: Gilead: Consultancy. Hegenbart: Alnylam: Honoraria; Akcea: Honoraria; Janssen: Consultancy, Research Funding; Prothena: Research Funding; Pfizer: Consultancy, Honoraria. Schönland: Prothena: Honoraria, Other: Travel grants; Takeda: Honoraria, Other: Travel grants; Pfizer: Honoraria; Janssen: Honoraria, Other: Travel grants, Research Funding; Sanofi: Research Funding. Müller-Tidow: Pfizer: Research Funding; Bioline: Research Funding; Janssen: Consultancy, Research Funding. Dreger: Riemser: Consultancy, Research Funding, Speakers Bureau; Bluebird Bio: Consultancy; Roche: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; BMS: Consultancy; AstraZeneca: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Janssen: Consultancy; Gilead Sciences: Consultancy, Speakers Bureau. Schmitt: MSD: Membership on an entity's Board of Directors or advisory committees; Hexal: Other: Travel grants, Research Funding; Kite Gilead: Other: Travel grants; TolerogenixX: Current holder of individual stocks in a privately-held company; Bluebird Bio: Other: Travel grants; Novartis: Other: Travel grants, Research Funding; Apogenix: Research Funding. Schmitt: Therakos/Mallinckrodt: Research Funding; TolerogenixX Ltd: Current Employment; Jazz Pharmaceuticals: Other: Travel grant; Hexal: Other: Travel grant.

Sauer: Abbvie: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Matterhorn Biosciences AG: Consultancy, Other: DSMB/SAB Member; Takeda: Consultancy, Other: DSMB/SAB Member. Schubert: Gilead: Consultancy. Müller-Tidow: Janssen: Consultancy, Research Funding; Bioline: Research Funding; Pfizer: Research Funding. Schmitt: TolerogenixX: Current holder of individual stocks in a privately-held company; Novartis: Other: Travel grants, Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees; Kite Gilead: Other: Travel grants; Apogenix: Research Funding; Hexal: Other: Travel grants, Research Funding; Bluebird Bio: Other: Travel grants. Schmitt: Hexal: Other: Travel grant; Therakos/Mallinckrodt: Research Funding; Jazz Pharmaceuticals: Other: Travel grant; TolerogenixX Ltd: Current Employment.

Schubert: Gilead: Consultancy. Schmitt: TolerogenixX Ltd: Current Employment; Hexal: Other: Travel grant; Jazz Pharmaceuticals: Other: Travel grant; Therakos/Mallinckrodt: Research Funding. Müller-Tidow: Pfizer: Research Funding; Janssen: Consultancy, Research Funding; Bioline: Research Funding. Dreger: Riemser: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy; BMS: Consultancy; Gilead Sciences: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Bluebird Bio: Consultancy; Roche: Consultancy, Speakers Bureau. Schmitt: MSD: Membership on an entity's Board of Directors or advisory committees; TolerogenixX: Current holder of individual stocks in a privately-held company; Kite Gilead: Other: Travel grants; Bluebird Bio: Other: Travel grants; Novartis: Other: Travel grants, Research Funding; Hexal: Other: Travel grants, Research Funding; Apogenix: Research Funding.

Schmitt: Therakos Mallinckrodt: Other: Financial Support . Sellner:Takeda: Employment. Müller-Tidow:MSD: Membership on an entity's Board of Directors or advisory committees. Dreger:AbbVie, AstraZeneca, Gilead, Janssen, Novartis, Riemser, Roche: Consultancy; AbbVie, Gilead, Novartis, Riemser, Roche: Speakers Bureau; Neovii, Riemser: Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees, Other: Sponsoring of Symposia. Schmitt:Therakos Mallinckrodt: Other: Financial Support; MSD: Membership on an entity's Board of Directors or advisory committees, Other: Sponsoring of Symposia.

Müller-Tidow: MSD: Membership on an entity's Board of Directors or advisory committees. Dreger:Neovii, Riemser: Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees, Other: Sponsoring of Symposia; AbbVie, AstraZeneca, Gilead, Janssen, Novartis, Riemser, Roche: Consultancy; AbbVie, Gilead, Novartis, Riemser, Roche: Speakers Bureau. Schmitt:MSD: Membership on an entity's Board of Directors or advisory committees, Other: Sponsoring of Symposia; Therakos Mallinckrodt: Other: Financial Support. Schmitt:Therakos Mallinckrodt: Other: Financial Support.

Background:

Introduction