The review has been conducted by the Data Safety Monitoring Board (DSMB), an independent panel of specialists in the field. The reviewed data shows that in the first cohort comprising 3 patients treated, there was a good safety profile with no serious adverse events (SAEs) related to the WT1-TCR T cell therapy. Importantly, the therapy also met the protocol specified requirements for cell persistence, showing that the WT1 targeted T cells can survive and expand in patients.
Passing this first interim review has enabled the clinical trial to enter its second phase. Dosing has now successfully started in the second cohort of patients in the trial which allows patients to receive a higher dose of the gene modified WT1 TCR T cells.
The therapy uses TCR gene-modified T cells to target WT1-overexpressing cells. It involves modification by gene therapy of the patient's own T cells, so that they may recognise and destroy WT1-expressing cells when infused back into the body. It shows potential in disorders such as acute myeloid leukaemia and myelodysplastic syndrome and has been ranked by the US National Cancer Institute (NCI) as the number 1 target for cancer immunotherapy.
The trial is operated by Catapult Therapy TCR Limited, a company formed by the Cell and Gene Therapy Catapult with UCLB and Imperial Innovations to develop the T cell therapy, and is supported by the NIHR Biomedical Research Centre (BRC) at University College London Hospitals. Pre-clinical development of the TCR gene therapy programme was supported by Bloodwise, previously Leukaemia and Lymphoma Research. In August 2015 the Cell and Gene Therapy Catapult appointed Cellular Therapeutics Limited (CTL), as a manufacturer for the clinical trial.
“Developing TCR gene-modified T cells to target WT1-overexpressing cells continues to show promise as an immunotherapy for a range of cancers including the trials that we have underway in acute myeloid leukaemia and myelodysplastic syndrome,” said Keith Thompson, CEO, the Cell and Gene Therapy Catapult. “The progress of the WT1 TCR clinical trials supported by the positive DSMB review, is encouraging and we look forward to expanding these trials across the UK and Europe. Further results are expected during 2017.”
“We are delighted with the progress of this clinical trial in acute myeloid leukaemia,” said Professor Emma Morris, UCL Institute of Immunity and Transplantation, Chief Investigator and co-inventor as well as Director of the Infection, Immunity and Inflammation Programme at the National Institute for Health Research University College London Hospitals Biomedical Research Centre. “This is an important area of unmet medical need and we are progressing with the next stages of recruitment now ongoing in the second cohort of the AML trial.”
“We are pleased to note the progress of this innovative therapy,” said Tony Hickson, Managing Director of Technology Transfer at Imperial Innovations. “Catapult Therapy TCR is a great example of collaboration between UK universities and technology transfer organisations and we look forward to the results of forthcoming trials.”