Examining TRX103 Tolerance Against Transient Suppression in Mismatched HCT

According to Monzr M. Al Malki, MD, a combination of DC-10, FOXP3-positive, and natural type 1 regulatory (Tr1) regulatory T cells may be important to improving the outcomes of hematopoietic cell transplantation (HCT) and tolerizing the environment.

In an interview with CancerNetwork^®, Al Malki discussed a presentation he gave at the 2026 Tandem Meetings detailing the safety and tolerability findings from a first-in-human study of TRX103, a novel off-the-shelf allogeneic CD4 T-cell therapy, in patients with hematologic malignancies undergoing HCT. Specifically, he discussed how the infectious tolerance mechanism of TRX103 differs from the transient suppression seen with pharmacological agents such as posttransplant cyclophosphamide.

He began by highlighting a key finding of the study, in which a significant acceleration in immune reconstitution of donor-derived CD4-positive T cells was observed with the investigational agent. Al Malki further expressed that these T cells, in addition to FOXP3-positive and DC-10 regulatory cells, have shown levels higher than historical controls in institutional data. Moreover, he expressed that the increase in Tr1 cell levels that was reached exceeded that of healthy donors 42 days post transplant, indicating the pharmacokinetic potential of TRX103.

Al Malki is director of the Unrelated Donor Bone Marrow Transplant and Haploidentical Transplant programs and professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope.

Transcript:

Based on the data that we presented at the [2026 Tandem Meetings,] we saw significant accelerated immune reconstitution of donor-derived CD4-positive T cells. Those will reach higher levels compared with historical control, which we already published in City of Hope data. This was also the same for FOXP3-positive regulatory T cells.

We also saw increasing numbers of circulating, tolerogenic dendritic cells. We call them DC-10 [cells], which usually express CD14 and CD16, in parallel to the natural Tr1 cells increasing. The prompt increase reached the level that we see in even healthy donors in the 42 days post transplant. A combination of donor-derived DC-10, FOXP3-positive, and natural Tr1 regulatory T cells are usually important to tolerizing environment and improving the outcome of transplant.

Reference

Al Malki MM, Juckett M, Perales MA, et al. Off-the-shelf engineered Tr1 cells (TRX103) in patients with hematological malignancies undergoing HLA-mismatched hematopoietic cell transplantation (HCT) show safety and dose dependent effects. Abstract presented at: 2026 Transplantation & Cellular Therapy Meetings of American Society for Transplantation and Cellular Therapy and Center for International Blood and Marrow Transplant Research; February 4-7, 2026; Salt Lake City, UT. Abstract 8.