A GMP-Compliant Procedure for the Generation of Gene-Modified T cells.

The field of Adoptive Cell Therapy (ACT) has been revolutionized by the development of genetically modified cells, specifically Chimeric Antigen Receptor (CAR)-T cells. These modified cells have shown remarkable clinical responses in patients with hematologic malignancies. However, the high cost of producing these therapies and conducting extensive quality control assessments has limited their accessibility to a broader range of patients.

Hypomethylation-induced regulatory programs in T cells unveiled by transcriptomic analyses.

Regulatory T cells (Tregs) are essential mediators of tolerance mitigating aberrant immune responses. While naturally occurring Treg (nTreg) development and function are directed by epigenetic events, induced Treg (iTreg) identity and mechanisms of action remain elusive. Mirroring the epigenetic circuits of nTregs, we and others have used hypomethylation agents (HAs) to convert T cells into iTregs (HA-iTregs) and further showed that the suppressive properties of the HA-iTregs are predominantly confined in an emergent population, which expresses the immunomodulatory molecule HLA-G, consequently providing a surface marker for isolation of the suppressive HA-iTreg compartment (G cells).

Study protocol: Phase I/II trial of induced HLA-G regulatory T cells in patients undergoing allogeneic hematopoietic cell transplantation from an HLA-matched sibling donor.

Regulatory T-cell (Treg) immunotherapy has emerged as a promising and highly effective strategy to combat graft-versus-host disease (GvHD) after allogeneic hematopoietic cell transplantation (allo-HCT). Both naturally occurring Treg and induced Treg populations have been successfully evaluated in trials illustrating the feasibility, safety, and efficacy required for clinical translation. Using a non-mobilized leukapheresis, we have developed a good manufacturing practice (GMP)-compatible induced Treg product, termed iG-Tregs, that is enriched in cells expressing the potent immunosuppressive human leucocyte antigen-G molecule (HLA-G).

Correction to: Clinical-scale production of Aspergillus-specific T cells for the treatment of invasive aspergillosis in the immunocompromised host.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Clinical-scale production of Aspergillus-specific T cells for the treatment of invasive aspergillosis in the immunocompromised host.

Invasive aspergillosis (IA) represents a leading cause of mortality in immunocompromised patients. Although adoptive immunotherapy with Aspergillus-specific T cells (Asp-STs) represents a promising therapeutic approach against IA, the complex and costly production limits its broader application. We generated Asp-STs from a single blood draw of healthy individuals or IA patients in only 10 days, by either Aspergillus fumigatus (AF) lysate or peptide stimulation of mononuclear cells.