FDA Approves First Treg-Based Cell Therapy

The FDA has approved Tregzi, the first regulatory T cell-based immunotherapy for adult patients with blood cancers undergoing allogeneic hematopoietic stem cell transplantation.

The therapy, developed by Orca Biosystems, is approved to improve chronic graft-versus-host disease-free survival in adults with hematologic malignancies who receive an allogeneic stem cell transplant from an 8/8 HLA-matched related or unrelated donor.

The therapeutic modality is an allogeneic cellular immunotherapy composed of three donor-derived cell components: purified hematopoietic stem and progenitor cells, regulatory T cells, and conventional T cells. The approach is designed to reconstitute the patient’s blood-forming and immune systems while reducing the risk of chronic graft-versus-host disease, or GVHD.

The approval is supported by PRECISION-T, a randomized clinical trial involving 187 adults with blood cancers. At one year, 78 percent of patients who received Tregzi were alive without moderate or severe chronic GVHD, compared with 38.4 percent of patients who received a standard transplant. After accounting for death as a competing risk, serious chronic GVHD developed within one year in 12.6 percent of Tregzi-treated patients versus 44 percent of patients in the standard-transplant group. Source

Top FDA Cell and Gene Therapy Regulator to Step Down

Vijay Kumar is stepping down as acting director of the FDA office responsible for reviewing cell and gene therapies, adding to a period of leadership turnover at the agency.

Kumar had been serving as acting director of the Office of Therapeutic Products within the FDA’s Center for Biologics Evaluation and Research. The office oversees reviews of gene therapies, cell therapies, tissue-engineered products, and other advanced biologics.

Acting CBER Director Karim Mikhail will also serve as acting director of the Office of Therapeutic Products while the FDA searches for a permanent replacement. Source

Epigenetic Therapy Increases Muscle Volume in Early Trial

Epicrispr Biotechnologies has reported early clinical evidence that its investigational epigenetic therapy EPI-321 may increase lean muscle volume in patients with facioscapulohumeral muscular dystrophy.

The data come from an ongoing open-label Phase 1/2 first-in-human study in adults with FSHD, a progressive genetic neuromuscular disease driven by abnormal expression of DUX4. There are currently no approved disease-modifying therapies for the condition.

EPI-321 is designed to silence DUX4 using Epicrispr’s Gene Expression Modulation System platform. The single-dose therapy aims to durably regulate disease-causing gene expression without altering the underlying DNA sequence.

Nine patients have been treated across two dose cohorts. Among the first three evaluable patients in the lower-dose cohort, all showed gains in lean muscle volume at six months compared with baseline. The average increase was approximately 0.8 pounds of muscle mass. Source

CAR T Therapy Targets Mutation Driving Rare Blood Cancers

A new CAR T-cell therapy has been designed to selectively target the disease-driving cells behind a group of rare blood cancers known as myeloproliferative neoplasms.

The preclinical therapy, developed by researchers at University College London and the University of Oxford, targets mutant calreticulin, or mutCALR, a cancer-specific abnormal protein found in around a quarter to a third of patients with myeloproliferative neoplasms. 

Pathogenic CALR mutations produce an altered protein that forms a complex with the thrombopoietin receptor and appears on the surface of disease-driving cells. That creates a visible, cancer-specific target for engineered immune cells. The researchers developed CAR T cells designed to recognize this mutant CALR–thrombopoietin receptor complex. In laboratory experiments, the cells selectively killed mutCALR-positive cells while sparing JAK2-mutated myelofibrosis cells used as controls. The CAR T cells also depleted mutant stem and progenitor cells from patient samples without apparent activity against healthy stem cells.

In mouse xenograft models of mutCALR leukemia, treatment with the CAR T cells reduced leukemic burden and significantly prolonged survival compared with control CAR T cells. Source

CAR T Therapy Targets Brain Tumor Support System

A CAR T-cell therapy designed to attack both glioblastoma cells and the immune cells that help sustain them has shown strong activity in preclinical models of the deadly brain cancer.

The study focused on GPNMB, a cell-surface protein found on glioblastoma cells and on tumor-associated macrophages, an immune-cell population that can support tumor growth, suppress immune responses, and contribute to treatment resistance. By targeting both compartments at once, researchers at King’s College London and McMaster University aimed to treat glioblastoma as a connected tumor–immune ecosystem rather than as a mass of cancer cells alone.

The researchers engineered anti-GPNMB CAR T cells and tested them across several laboratory and animal models. Responses persisted beyond 160 days in six of seven mice in one model and beyond 120 days in all six mice in another. The CAR T cells also controlled tumors that had persisted after CD133-directed CAR T therapy, suggesting a possible role after antigen escape or prior treatment pressure. Source

Drug Switch Gives CRISPR On-Demand Control

Researchers have developed small-molecule-controlled CRISPR systems that allow genome editing to be switched on by drug inducers and kept largely inactive in their absence. The systems, called PRINCE and Little Prince, were designed to give therapeutic genome editing tighter temporal control by regulating both the nuclease protein and guide RNA expression. In human cells, PRINCE remained controllable after stable genomic integration and two years of culture: a 24-hour drug exposure activated editing, while uninduced cells showed minimal background activity.

To support in vivo delivery, the team developed Little Prince, a compact version based on miniature nucleases that can fit into a single adeno-associated virus vector. In a humanized mouse model of hypercholesterolemia, AAV8-delivered Little Prince targeted human PCSK9 in the liver. Drug induction reduced serum total cholesterol and LDL cholesterol by about 45 percent and 47 percent, respectively, while uninduced mice showed background editing comparable to negative controls. In a separate humanized mouse model of neovascular age-related macular degeneration, Little Prince targeted VEGFA in the retina, reducing vascular leakage and lesion size and improving retinal function. Source

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