Dr Bertaina on T-allo10 Infusion in Young Patients With Hematologic Malignancies

Alice Bertaina, MD, PhD, co-director, Bass Center for Childhood Cancer and Blood Diseaeses, section chief, Stem Cell Transplant and Regenerative Medicine, medical director, Inpatient Services, Lucile Packard Children's Hospital, Stanford University; Lorry I. Lokey Faculty, Pediatrics - Stem Cell Transplantation, Division of Pediatric Hematology, Oncology, Stem Cell Transplantation & Regenerative Medicine, Stanford Medicine, discusses the utility of T-allo10 infusion post TCRαβ-positive T-cell and CD19-positive B-cell-depleted (αβdepleted)–hematopoietic stem cell transplantation (HSCT) in young patients with hematologic malignancies.

Investigators of a phase 1 trial (NCT04640987) combined αβ-depleted HSCT with a newly developed T-cell immunotherapy, T-allo10, which is produced from donor CD4-positve T cells and enriched in type 1 regulatory T (Tr1) cells that specifically target host alloantigens to suppress host-reactive TCRαβ-positive T cells, thereby preventing GVHD. Investigators hypothesized that infusing T-allo10 following αβ-depleted HSCT would expedite immune reconstitution by providing a source of TCRαβ-positive T cells to support immune responses. This treatment approach was also expected to modulate anti-host immune responses through the function of alloantigen-specific Tr1 cells.

Notably, this trial demonstrated particularly promising outcomes given the high-risk nature of the patient population, Bertaina begins. For instance, investigators observed successful survival outcomes without severe acute or chronic GVHD post-transplantation, Bertaina states.

The investigators’ hypothesis was supported by findings showing an expansion of the Tr1 cell population shortly after infusion, reaching a peak between days 1 and 7, with persistent effects observed over longer follow-up periods, she continues. Additionally, oncologists observed significant improvements in CD19 immune reconstitution, particularly in the memory compartment, contributing to naive immune reconstitution, Bertaina adds. Furthermore, T-allo10 infusion was associated with a trend toward reduced viral infections compared with historical controls, she concludes.

Overall, the phase 1 results of this clinical trial demonstrate the efficacy of T-allo10 infusion in enhancing immune reconstitution and minimizing GVHD risk in pediatric and young adult patients with hematologic malignancies post–αβdepleted-HSCT.