Achilles Therapeutics, An Immunotherapy Spin-Out from Francis Crick Institute and UCL Cancer Institute, Targets Clonal Neoantigens in New Personalized Therapy for Melanoma

On May 29, 2020, it was announced that Achilles Therapeutics(, a UK-based company built on the research of Francis Crick institute ( roup Leader Charles Swanton (, PhD, and Sergio Quezada (, PhD, and Karl Peggs (, MD, at the University College London (UCL) Cancer Institute (, has started a clinical trial for a new personalized immunotherapy for patients with melanoma. The Phase I/II trial is testing a clonal neoantigen T cell (cNeT) therapy in approximately 20 patients with recurrent or metastatic melanoma. The first patient to take part in this trial received treatment in the week of this announcement. This new therapy uses T lymphocytes to target cancer-cell-surface antigens coded for by DNA mutations present in all the cancer cells of a cancer in a particular patient, regardless of where these cancer cells are in the body. This is possible because, while a cancer grows in a particular patient and mutates its DNA, all the resulting cancer cells in that patient retain the earliest mutations present in the trunk of the tumor’s evolutionary tree, and some of these mutations code for antigens that are expressed on the cancer cell surface. These are called clonal neoantigens. T lymphocytes recognize these markers as a sign that they need to attack the cell. The researchers will carefully select the particular lymphocytes used for each patient that recognize these clonal neoantigens that are unique to each person’s cancer.
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