Adoptive transfer of donor B lymphocytes: a phase 1/2a study for patients after allogeneic stem cell transplantation.

Winkler J, Tittlbach H, Schneider A, Vasova I, Strobel J, Herold S, Maas S, Spriewald B, Repp R, Kordelas L, Mach M, Wolff D, Edinger M, Mackensen A, Winkler T (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Blood Advances American Society of Hematology

Book Volume: 8

Pages Range: 2373-2383

Journal Issue: 10

DOI: 10.1182/bloodadvances.2023012305

Abstract

Immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is slow and patients carry a high and prolonged risk of opportunistic infections. We hypothesized that the adoptive transfer of donor B cells can foster after HSCT immuno-reconstitution. Here, we report, to our knowledge, the results of a first-in-human phase 1/2a study aimed to evaluate the feasibility and safety of adoptively transferred donor B cells and to test their activity upon recall vaccination. Good manufactoring practice (GMP) B-cell products were generated from donor apheresis products using 2-step magnetic cell separation. Fifteen patients who had undergone allo-HSCT were enrolled and treated after taper of immunosuppression (median, day +148; range, 130-160). Patients received 4 different doses of B cells (0.5 × 106 to 4.0 × 106 B cells per kg body weight). To test the activity of infused donor memory B cells in vivo, patients were vaccinated with a pentavalent vaccine 7 days after B-cell transfer. We observed the mobilization of plasmablasts and an increase in serum titers against vaccine antigens, with a stronger response in patients receiving higher B-cell numbers. Analysis of immunoglobulin VH-sequences by next-generation sequencing revealed that plasmablasts responding to vaccination originated from memory B-cell clones from the donor. Donor B-cell transfer was safe, as no Epstein-Barr virus (EBV) reactivation was observed, and only low-grade graft-versus-host disease (GVHD) occurred in 4 out of 15 patients. This pilot trial may pave the way for further studies exploring the adoptive transfer of memory B cells to reduce the frequency of infections after allo-HSCT. This trial was registered at ClinicalTrial.gov as #NCT02007811.

Authors with CRIS profile

Julia Winkler Department of Medicine 5 – Haematology and Oncology Hannes Tittlbach Lehrstuhl für Innere Medizin V Andrea Schneider Lehrstuhl für Genetik Ingrid Vasova Lehrstuhl für Innere Medizin V Julian Strobel Department of Transfusion Medicine and Haemostaseology Susanne Herold Medizinische Fakultät Bernd Spriewald Department of Medicine 5 – Haematology and Oncology Michael Mach Medizinische Fakultät Andreas Mackensen Lehrstuhl für Innere Medizin V Thomas Winkler Professur für Genetik

Involved external institutions

Städtisches Krankenhaus Kiel DE Germany (DE) Universitätsklinikum Essen DE Germany (DE) Universitätsklinikum Regensburg DE Germany (DE)

How to cite

APA:

Winkler, J., Tittlbach, H., Schneider, A., Vasova, I., Strobel, J., Herold, S.,... Winkler, T. (2024). Adoptive transfer of donor B lymphocytes: a phase 1/2a study for patients after allogeneic stem cell transplantation. Blood Advances, 8(10), 2373-2383. https://doi.org/10.1182/bloodadvances.2023012305

MLA:

Winkler, Julia, et al. "Adoptive transfer of donor B lymphocytes: a phase 1/2a study for patients after allogeneic stem cell transplantation." Blood Advances 8.10 (2024): 2373-2383.

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