For years one of the biggest hurdles in the search for an effective cancer treatment was the inability to differentiate cancer cells from normal cells. Chemotherapy, the first-line treatment for most types of cancers, indiscriminately targets all rapidly dividing cells in our body irrespective of whether they are cancerous or normal e.g. intestinal tract cells, hair cells, skin cells and blood cells. Similarly, radiotherapy also impacts normal cells leading to many adverse effects.
What is cancer immunotherapy?
Immunotherapy has become an established fourth pillar of cancer treatment alongside chemotherapy, radiotherapy and surgery. Over the last decade, we have witnessed many breakthroughs in this field. FDA-approved immunotherapies have become available for over a dozen types of cancers. James P. Allison and Tasuku Honjo were awarded the Nobel Prize for their groundbreaking work on checkpoint inhibitors targeting immune regulators that dampen the immune response to a foreign stimulus. The discovery of T-cell checkpoint pathways and inhibitors has driven scientists to better understand how the immune system can recognise cancer cells.
The discovery of neoantigens
A significant development within cancer immunotherapy has been the discovery of neoantigens. Neoantigens are peptides or fragments of protein found on the cancer cell surface due to genetic mutations. These are optimal therapeutic targets as they are selectively present on the cancer cell surface and not on normal cells. Neoantigens are unique to every single patient and next generation sequencing has now made it possible to identify the mutations present in every cancer cell of every patient.
A personalised approach to attack cancer
Biopharmaceutical companies are working on new approaches within cancer immunotherapy such as neoantigen-targeting vaccines and adoptive cellular therapies, which are both patient and tumour specific. Companies like Achilles Therapeutics are currently developing personalised T cell therapies targeting neoantigens. Their approach involves sequencing and identification of patient and tumour-specific neoantigens. It also involves extracting, isolating and re-engineering tumour infiltrating lymphocytes (TILs) enhancing their ability to recognise neoantigens on the cancer cells. Once neoantigen-targetting TILs are infused back into the patient, they are able to recognise and remove the tumour.
The ability to sequence cancer genomes, identify targets specific to each cancer patient and reengineer their own immune system to attack the tumour is a revolutionary step towards personalised medicine.
A final note
The concept of personalised medicine is not new – its core principles have been present since the 1960s and the term first appeared in publications in 1999 (Langreth and Waldholz, 1999). However, the integration of scientific and technological advances such as sequencing cancer genomes and the development of algorithms for epitope prediction now accelerate the progress of truly personalised therapies.