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

Abstract

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: Julia Winkler, Hannes Tittlbach, Andrea Schneider, Ingrid Vasova, Julian Strobel, Susanne Herold, Stefanie Maas, Bernd M Spriewald, Roland Repp, Lambros Kordelas, Michael Mach, Daniel Wolff, Matthias Edinger, Andreas Mackensen, Thomas H Winkler
• Journal: Blood advances (Blood Adv) Vol. 8 Issue 10 Pg. 2373-2383 (May 28 2024) ISSN: 2473-9537 [Electronic] United States
• PMID: 38467031 (Publication Type: Journal Article, Clinical Trial, Phase I, Clinical Trial, Phase II)
• Copyright: © 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Topics

• Humans
• Hematopoietic Stem Cell Transplantation (methods, adverse effects)
• Adult
• B-Lymphocytes (immunology)
• Middle Aged
• Male
• Female
• Transplantation, Homologous
• Adoptive Transfer (methods)
• Tissue Donors
• Young Adult
• Graft vs Host Disease (etiology, prevention & control)