A team of London-based academics is set to study a stem cell-delivered gene therapy in patients with lung cancer. The 56-person trial is the first time a stem cell-gene therapy combination has been tested in humans in the U.K.
University College London's Professor Sam Janes will lead the study, which builds on preclinical work he and his collaborators published late last year. The paper showed the potential of engineering mesenchymal stromal cells to overexpress tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). When administered to mice with mesothelioma, the stem cell-gene therapy combo was associated with a drop in tumor burden and an uptick in the apoptosis process that is triggered by the TRAIL protein.
Now, the researchers have snagged £2 million ($3 million) from the Medical Research Council (MRC) to investigate whether combining the treatment with chemotherapy results in better outcomes than the standard of care. The clinical trial will give almost one billion of the engineered, TRAIL-expressing stem cells to each of the 56 lung cancer patients that participate. Each patient will receive three infusions, three weeks apart and one day after they are treated with chemotherapy.
The objective is to assess how the treatment compares to standard of care. If the data are favorable, they could lead to the treatment advancing into larger lung cancer trials and the therapeutic approach being applied to other indications. Several features of the treatment make it attractive for such an expansion. Notably, the stem cells don't need to come from a relative or tissue match because the comparative lack of proteins on their surface means the body doesn't mount an immune response.
Material inside the cell is protected from degradation, theoretically allowing the TRAIL protein to reach target receptors and trigger apoptosis. Other attempts to deliver TRAIL have faltered because the protein was denatured before it reached its target. If the stem cell delivery vehicle provides a way around these defenses, it could enable TRAIL to trigger apoptosis in a range of cancers. For now, that "if" remains a sizable unknown. "This is truly experimental," Janes told The Guardian.