Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies.

Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy trials. The trials employed integrating gammaretroviral or lentiviral vectors to deliver engineered receptors to target HIV-1 infection or cancer.

Stem Loop Mediated Transgene Modulation in Human T Cells.

Controlling gene expression is useful for many applications, but current methods often require external user inputs, such as the addition of a drug. We present an alternative approach using cell-autonomous triggers based on RNA stem loop structures in the 3' untranslated regions (UTRs) of mRNA. These stem loops are targeted by the RNA binding proteins Regnase-1 and Roquin-1, allowing us to program stimulation-induced transgene regulation in primary human T cells.

CAR T cells in autoimmune disease: On the road to remission.

Several recent reports have demonstrated that B cell-targeting chimeric antigen receptor (CAR) T cells offer a viable treatment option for patients with autoantibody-mediated autoimmune diseases. To present additional data on this therapy and discuss strategies for more efficient clinical translation, leading experts in CAR T cell therapy for autoimmunity from various countries, including China, Germany, and the United States, convened at the "1st International Autoimmune CAR T Innovators Summit" in Grassau, Germany, from May 10-12, 2024. The summit showcased additional insights of CAR T cell therapy in diverse autoimmune diseases and provided platforms for discussions on key questions through workshops and roundtables.

Beyond the blood: expanding CAR T cell therapy to solid tumors.

Chimeric antigen receptor (CAR) T cell therapy stands as a transformative advancement in immunotherapy, triumphing against hematological malignancies and, increasingly, autoimmune disorders. After a decade of relatively modest results for solid tumors, recent clinical trials and patient reports have also started to yield promising outcomes in glioblastoma and other challenging solid tumor entities. This Perspective seeks to explore the reasons behind these latest achievements and discusses how they can be sustained and expanded through different strategies involving CAR engineering and synthetic biology.