https://orcid.org/0000-0002-1117-0350
Key Points
No clinically significant EBV reactivation nor acute or chronic GvHD occurred after adoptive donor B cell transfer into allo-SCT recipients
Transferred donor B cells enhance the memory antibody response against vaccine antigens
Immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is slow and patients carry a high and prolonged risk for opportunistic infections. We hypothesized that the adoptive transfer of donor B cells can foster post-HSCT immuno-reconstitution. Here we report on the results of a first-in-human phase I/IIa study aimed to evaluate the feasibility and safety of adoptively transferred donor B cells and to test their activity upon recall vaccination. GMP-grade B-cell products were generated from donor apheresis products using a two-step magnetic cell separation. 15 allo-HSCT patients were enrolled and treated after taper of immunosuppression (median day +148, range 130 to 160). Patients received four different doses of B cells (0.5x106 - 4.0x106 B-cells per kg body weight (BW)). 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 mobilization of plasmablasts and an increase of serum titers against vaccine antigens with a stronger response in patients receiving higher B cell numbers. The analysis of immunoglobulin VH-sequences by next-generation-sequencing revealed that plasmablasts responding to the vaccination originated from memory B cell clones from the donor. Donor B cell transfer was safe as no EBV reactivation was observed, and only low-grade 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 NCT02007811
