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 Tr1 T-regulatory 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 Meeting 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 does the infectious tolerance mechanism of TRX103 differ from the transient suppression seen with pharmacological agents like post-transplant 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 cells levels reached exceeded healthy donors 42-post transplant, indicating the pharmacokinetic potential of TRX103.

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

Transcript:

Based on the data that we presented in 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 that we already published in City of Hope data. This was also the same for FOXP3-positive T regulatory cells.

We also saw increasing numbers of circulating, tolerogenic dendritic cells. We call them DC 10, 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 donor in the 42 days post-transplant. A combination of donor-derived DC 10, FOXP3-positive and natural Tr1 T-regulatory cells are usually important to tolerizing environment and improve 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. Presented at: 2026 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; February 4-7, 2026; Salt Lake City, UT. Abstract 8