Safety and feasibility of HA-1 TCR-T post-HSCT for recurrent leukemia
Krakow EF, Brault M, Summers C, et al. HA-1-Targeted T Cell Receptor (TCR) T Cell Therapy for Recurrent Leukemia After Hematopoietic Stem Cell Transplantation. Blood. 2024; (doi: 10.1182/blood.2024024105).
Findings from a Phase I clinical trial indicate that targeting HA-1 — a type of minor histocompatibility antigen — is a safe, tolerable, and may be effective against leukemia relapse following allogeneic hematopoietic stem cell transplantation (HSCT). For the study, researchers administered infusions of CD8+ and CD4+ T cells expressing an HA-1-specific T cell receptor (TCR) plus a CD8 co-receptor to nine transplant recipients who experienced disease recurrence after HSCT. The TCR-T cells were manufactured from HA-1 disparate transplant donors. Tthe trial was the first to use them in tandem with a CD8 co-receptor in order to enable antigen-specific CD4+ T cell function. The cells expanded and persisted in vivo following adoptive transfer. While primary feasibility and tolerability outcomes were achieved, the investigation was not designed to evaluate efficacy. The researchers report that 4 of the 9 study participants attained or maintained complete remission after lymphodepletion and receiving HA-1 TCR-T.