The UCL/UCLH BRC has supported a major collaborative effort to better understand the biology of non-small cell lung cancer (NSCLC) to improve treatment and patient outcomes. NSCLC accounts for about 80% of all lung cancers. If it spreads to other organs or tissues in the body, survival is less than 20% five years after diagnosis. A spin-out company, Achilles, was launched in 2016 to develop personalised therapies based on this research.
The TRACERx lung cancer consortium was established by Professor Swanton (2014). The study tracks NSCLC from diagnosis to treatment in 842 patients and has established the critical importance of how cancers evolve and genetic diversity of cancer cells if they become drug resistant 1. Genetic changes responsible for lung cancer have been characterised and mutations, present in all tumour cells which produce cancer-specific proteins (known as clonal neoantigens) have been identified using newly-developed algorithms 2. Neoantigens which arise at the beginning of a tumour’s existence are present on all virtually all the cancer cells but not on healthy cells, so could allow scientists to target tumours with immune therapies without harming healthy tissues. As tumours progress, cells within them mutate further, allowing them to better grow, spread, avoid detection by the body’s immune system and evolve resistance to chemo or immunotherapy 3.
Current UCL trials are evaluating the impact of a series of drugs targeted at the specific mutations present in any individual. Neoantigen-specific T cells in patients’ tumours and blood have been identified and isolated, and the cultivation of such cells in the lab has been optimised (Quesada and Peggs). Achilles Therapeutics Ltd was established to scale up these procedures and to take clonal neoantigen specific T-cells (cNeTs) into the clinic. To date, Achilles has attracted £127M funding which has enabled the research to progress rapidly into clinical trials for both lung cancer (CHIRON trial) and melanoma (THETIS trial). Achilles identifies clonal neoantigens specific to an individual which are present on virtually all of their cells. Tcells taken from patients are expanded in the lab and then reinfused into the patient where they target the tumour cells.
The development of such immunotherapies has the potential to save many lives of patients with multiple types of tumour.
1. Abbosh et al Nature 2017; 2. Rosenthal et al Nature 2019; 3. Litchfield et al Cell 2021
