Next generation cancer immunotherapy - Achilles Therapeutics
Although tumours start off from a single mutated cell they can grow to around a trillion cells. And as the cells grow and divide, they evolve and accumulate many more mutations. This evolutionary process creates different populations of cells in a tumour, leading to vast cellular and mutational diversity. This makes it almost impossible to eliminate every single cancer cell in the body with therapies that exist today.
But advances in DNA sequencing now allow scientists to identify all the mutations within a tumour. Achilles scientists are able to use this information to trace back all the evolutionary steps in a patient’s tumour and to create an evolutionary tree of the cancer. We can identify the earliest mutations that are there from the very start of a cancer’s evolution. These early trunk mutations are still present in all the different populations of cancer cells. And we can differentiate these from the branch mutations that are only present in some cell populations within the tumour.
No two tumours evolve in the same way, which is why we must analyse the tumour DNA for each patient, to map their cancer’s evolutionary tree. The genetic differences within a tumour lead to a mutation signature on a cell’s surface, which can be targeted by the immune system Importantly, this signature is not present on healthy cells. Using this signature, scientists can attack a tumour with immune therapy based on one or more mutations. But picking the right mutations is vital.
If these mutations are in the branches of cancer’s evolutionary tree, the immune system will only target the parts of the tumour with that particular mutation, and the rest will continue to grow. Because Achilles scientists can create an evolutionary tree of the cancer, we can identify truncal mutations that are present in all cancer cells within a patient. We can make immune therapies that are directed at these truncal mutations and will target every cancer cell in the body, while sparing healthy tissue.
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