Immune Reconstitution Profiling Suggests Antiviral Protection after Transplantation with Omidubicel: A Phase 3...

Area of Science:

• Immunology
• Hematology
• Cell Therapy

Background:

• Allogeneic hematopoietic cell transplantation (HCT) is a vital treatment for hematologic disorders.
• Rapid immune reconstitution (IR) post-HCT is linked to better clinical outcomes and fewer infections.
• Omidubicel, a novel cell therapy from umbilical cord blood (UCB), demonstrated faster hematopoietic recovery in a Phase 3 trial.

Purpose of the Study:

• To systematically characterize and compare immune reconstitution kinetics between omidubicel and standard UCB transplantation.
• To investigate the association between immune reconstitution patterns and clinical outcomes, including infection rates.

Main Methods:

• A prospective substudy of a global Phase 3 trial involving 37 patients (17 omidubicel, 20 UCB).
• Longitudinal peripheral blood sampling at 10 time points (7-365 days post-HCT).
• Flow cytometry, T cell receptor excision circle quantification, and T cell receptor sequencing to assess immune cell populations and diversity.

Main Results:

• Omidubicel recipients showed significantly faster IR of lymphoid and myelomonocytic subpopulations compared to UCB recipients, particularly within 14 days post-HCT.
• Marked increases in median helper T (Th) cell and natural killer (NK) cell counts were observed in omidubicel recipients within 1-3 weeks post-HCT.
• Early reconstitution of NK and Th cells correlated with a decreased incidence of post-HCT viral infections.

Conclusions:

• Omidubicel promotes rapid and broad immune reconstitution across multiple immune cell types, including T cells, B cells, NK cells, and dendritic cells.
• The enhanced IR with omidubicel, particularly early NK and Th cell recovery, may contribute to reduced post-transplant infections.
• Omidubicel offers a balanced cellular composition and diverse T cell receptor repertoire, supporting robust immune recovery.