Distinct in vivo dynamics of donor-derived stem cell memory CAR T cells post-allogeneic HSCT relapse
Summary
Donor-derived CD19-CAR T cells offer a therapeutic option for B cell malignancies relapsing after allogeneic hematopoietic stem cell transplantation but are often constrained by poor engraftment, expansion, and persistence. In a first-in-human study (NCT01087294), we found that CAR-modified stem-cell memory T (TSCM) cells exhibited greater expansion and persistence than standard CAR T cells, enabling complete responses at low doses in the absence of lymphodepletion. CAR TSCM cells induced
Content
# Distinct in vivo dynamics of donor-derived stem cell memory CAR T cells post-allogeneic HSCT relapse
*Published: 2026 Apr 30*
Donor-derived CD19-CAR T cells offer a therapeutic option for B cell
malignancies relapsing after allogeneic hematopoietic stem cell transplantation
but are often constrained by poor engraftment, expansion, and persistence. In a
first-in-human study (NCT01087294), we found that CAR-modified stem-cell memory
T (TSCM) cells exhibited greater expansion and persistence than standard CAR T
cells, enabling complete responses at low doses in the absence of
lymphodepletion. CAR TSCM cells induced mild cytokine-release syndrome,
dominated by IFN-γ. Both products differentiated into effectors; however, only
CAR TSCM cells robustly reconstituted the stem-like compartment over time. CAR
TSCM cells were sustained through clonal succession, whereas persisting standard
CAR T cells resulted from maintenance or contraction of early-expanded clones.
While poor expansion limited standard CAR T cell activity, resistance to CAR
TSCM cells was driven primarily by tumor- and host-related factors. These
findings establish CAR TSCM cells as a promising platform for next-generation
CAR T cell therapies.
DOI: 10.1016/j.cell.2026.03.047