Veto Cells Tested With Haploidentical T-Cell-Depleted HSCT

By Dustin Samples - Last Updated: December 11, 2022

Nonmyeloablative (NMA) haploidentical T-cell-replete hematopoietic stem cell transplantation (HSCT) is a common therapy to combat hematologic malignancies. T cells, however, can cause graft-versus-host disease (GVHD), so immunosuppression is required.

As an alternative, megadoses of haploidentical hematopoietic stem cells depleted of T cells can be used to avoid immunosuppressive therapy. This methodology carries low risk of GVHD, but engraftment is hard to achieve.

Researchers at The University of Texas MD Anderson Cancer Center in Houston believe they have developed a workaround. They presented their findings at the 64th American Society of Hematology Annual Meeting and Exposition.

Veto donor cells act as a target for host T cells. The veto cells attract and destroy the host T cells before the host cells can attack and reject the transplant cells. Using T-cell-depleted megadose haploidentical HSCT in combination with veto cells, the research team has previously demonstrated feasibility in fully mismatched recipient mice. They have now moved from preclinical models to their first human trial.

A total of 9 patients participated in this first-of-its-kind phase I clinical trial (hematologic malignancy, n=8; aplastic anemia, n=1).

By Day 30, all patients who received the study treatment had achieved engraftment, with only 1 patient experiencing GVHD (grade II of the skin). No toxicity was attributed to the veto cells. The only immunosuppression used in this study was cyclophosphamide given on days 3 and 4.

One patient who also had prior kidney transplantation from the same donor was able to discontinue immunosuppressive therapy without transplant rejection.

Limit dilution analysis via enzyme-linked immunospot assay demonstrated that host antidonor T cells tolerated human leukocyte antigens from the donor.

“This approach deserves further study in allogeneic HSCT for malignant and nonmalignant hematologic diseases, as well as enhancement of tolerance for organ transplantation,” concluded the researchers.

Champlin RE, Bachar Lustig E, Bashir Q, et al. First in human study of anti-viral veto cells enabling successful engraftment without severe Gvhd in non-myeloablative T cell depleted haploidentical hematopoietic stem cell transplantation (HSCT). Abstract #875. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.

Post Tags:ASH Annual Meeting 2022