Surgeons will remove a patient’s own immune cells from their ovarian tumour, supercharge them in the lab, and infuse them back to attack the cancer. Ovarian cancer is often diagnosed late and tends to return after standard treatment. Existing immunotherapies like CAR-T cells can cause severe side effects and often fail against solid tumours. Tumour infiltrating lymphocytes (TILs) are naturally occurring immune cells that recognise a patient’s unique cancer mutations. Instil Bio UK has developed methods to make these cells survive longer, multiply more aggressively, and produce more immune-signalling molecules once reinfused. If this engineered TIL therapy proves safe and effective in the planned US and UK clinical trial, it could offer a genuinely personalised treatment for metastatic ovarian cancer and other solid tumours. Unlike CAR-T cells, these TILs retain their natural specificity, which should reduce toxic side effects. The project also builds on the UK’s new Advanced Therapy Treatment Centres, creating the infrastructure needed to deliver such complex cell therapies at scale. The initial phase involves final pre-clinical development and establishing a robust manufacturing process before the trial begins.
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Tumour infiltrating lymphocytes (TILs) hold great promise as the basis of treatment for solid cancers. They target cancer specific mutations and are thus truly specific, reducing risk of toxicities and their polyclonal nature limits the emergence of resistance to therapy. TIL therapy has been tested extensively in melanoma and recent establishment of Advanced Therapy Treatment Centres in the UK will develop a streamlined infrastructure and pathway for adoption of Advanced Therapies such as TIL therapy. Importantly, TIL infiltration of the tumour strongly correlates with good outcome in a range of solid tumours and it has been shown that TIL can be isolated from tumour removed during routine surgery to reduce tumour burden in around 90% of patients. Importantly Instil Bio UK (Instil) has developed methods to enhance the efficacy of TIL and as a result of this project Instil will seek to test the safety and efficacy of engineered TIL therapy in metastatic Ovarian Cancer and a range of other solid tumours. The initial phase of the project will focus on the final pre-clinical development of the engineered TIL approach, followed by the development of a robust clinical manufacturing process and then the initiation of a clinical trial in the US and UK. The key attributes of Instil’s engineered TIL will be better survival of the cells, enhanced ability to expand in the patient and increased production of signalling molecules which mediate further immune response. These attributes are anticipated to enhance the effectiveness whilst retaining the natural specificity of TIL and hence not producing the toxicity seen with CAR-T/ TCR engineered T-cells.
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