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Gene-targeted therapy successful in treating 'undruggable' colon cancer

12 December 2016
Appeared in BioNews 881

Researchers have successfully treated a woman with cancer using her own immune cells to target a cancer-causing gene that had previously been considered 'undruggable'.

Although the study only involved one patient – 50-year-old Celine Ryan, who had advanced colon cancer that had spread into her lungs – the gene targeted is thought to drive 95 percent of all pancreatic cancers and 45 percent of all colorectal cancers.

The mutant gene, called KRAS, is part of a family of mutations that collectively cause more than 30 percent of all human cancers. Attempts to target these mutations with drugs have so far been unsuccessful.

Researchers at the US National Cancer Institute isolated immune cells from Ryan's tumours, which had the mutation G12D, which is seen in around 13 percent of colorectal cancer patients. They then grew 100 billion of these cells – called tumour-infiltrating lymphocytes (TILs) – and injected them into her bloodstream, along with interleukin-2, which stimulate these immune cells. All seven of her tumourS disappeared with the treatment.

The results were published in the New England Journal of Medicine.

'This study demonstrates for the first time that this method of administering TILs, called adoptive T-cell transfer immunotherapy, can mediate effective anti-tumour immune responses against cancers that express the KRAS G12D mutation,' explained Dr Steven Rosenberg of National Cancer Institute's Centre for Cancer Research, who led the study.

TILs are T-killer cells that have surface proteins (receptors) which attach onto proteins on the surface of cancer cells, known as tumour antigens, marking them for attack by the immune system. 'We have also identified multiple T-cell receptors that recognise this KRAS product, thus opening the possibility of T-cell receptor gene therapy against multiple types of cancer that express this common mutation,' added Dr Rosenberg.

Dr Carl June of the University of Pennsylvania, who was not involved in the study, said to the New York Times: 'It has huge implications. Every single pancreatic cancer patient has KRAS.' The big question, he added, is whether this case is 'one in a million, or something that can be replicated and built upon'.

The approach has already shown success in treating advanced melanoma, a type of skin cancer. Dr Rosenberg has achieved long-term remissions in 20 to 25 percent of the patients he has treated.

1 Patient, 7 Tumors and 100 Billion Cells Equal 1 Striking Recovery
New York Times |  7 December 2016
Cancer Breakthrough Aids One Patient, Raises Hopes for Many
Wall Street Journal |  7 December 2016
Cellular immunotherapy targets a common human cancer mutation
National Institutes for Health (press release) |  7 December 2016
Drugging the Undruggable Ras - Immunotherapy to the Rescue?
NEJM (editorial) |  8 December 2016
T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer
NEJM |  8 December 2016
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