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

Commentary
Video

Alice Bertaina MD, PhD, discusses T-allo10 infusion post–aβdepleted-HSCT 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.

Related Videos
Petros Grivas, MD, PhD, professor, Clinical Research Division, Fred Hutchinson Cancer Center; professor, Division of Hematology and Oncology, University of Washington (UW) School of Medicine; clinical director, Genitourinary Cancers Program, UW Medicine
Somedeb Ball, MBBS, assistant professor, medicine, Division of Hematology Oncology, Department of Medicine, Vanderbilt University Medical Center
Phillip J. Koo, MD
Gabriella Smith, MD
Mikkael A. Sekeres, MD, MS
Francesco Di Meo, PhD
Ko Un “Clara” Park, MD
Naseema Gangat, MBBS
Erin Frances Cobain, MD
Pashtoon Murtaza Kasi, MD, MS