An international team lead by British researchers has discovered cancer’s “Achilles heel” — an advance being hailed as a breakthrough that opens the door to new ways to harness the immune system in personalized cancer therapies.
The discovery, published in the journal Science, points the way to priming the immune system to target and destroy cancer cells by identifying specific antigens on their surface,
Medical News Today reports.
The research team determined how T cells — white blood cells that help the body fight cancer and infection — can recognize antigens that represent genetic mutations in tumors and target them like lethal homing devices.
Charles Swanton, of the University College London Cancer Institute in the UK, and colleagues said the findings represent a huge step forward in the emerging field of immunotherapy — in which a patient's own immune cells are enlisted to combat cancer.
"For many years we have studied how the immune response to cancer is regulated without a clear understanding of what it is that immune cells recognize on cancerous cells," said co-researcher Dr. Sergio Quezada, head of the Immune Regulation and Cancer Immunotherapy Laboratory at the UCL Cancer Institute.
"Based on these new findings, we will be able to tell the immune system how to specifically recognize and attack tumors."
Nearly 1.7 million new cancer cases are diagnosed in the U.S. every year; about 595,690 die from the disease annually.
The UCL researchers explained that as a tumor grows, it produces mutations that in turn produce antigens that act as "flags" for T cells, prompting them to launch an attack. But tumors also mount defenses to outwit and outrun the body's natural defenses.
"Genetically diverse tumors are like a gang of hoodlums involved in different crimes - from robbery to smuggling. And the immune system struggles to keep on top of the cancer — just as it's difficult for police when there's so much going on," explained Dr. Quezada.
For the new study, the researchers pinpointed unique antigens that arise on the surface of cancer cells by analyzing the genetic data of more than 200 patients with lung cancer.
The team then isolated T cells from the tumors of two lung cancer patients and found they were able to recognize these common antigens. While the T cells were unable to kill the cancer cells, the researchers believe it may be possible to engineer them to do so and also to target all of the tumors at once.
For example, a vaccine could be developed that switches on these T cells in a cancer patient, or it may be possible to harvest and re-infuse a patient's own reengineered T cells back into their bodies to target the cancer cells.
"Our research shows that instead of aimlessly chasing crimes in different neighborhoods, we can give the police the information they need to get to the kingpin at the root of all organized crime - the weak spot in the patient's tumor — to wipe out the problem for good," said Dr. Quezada.
Swanton added: "There was evidence that complex tumors with many mutations could increase the chance of the immune system spotting them; now we can prioritize and target tumor antigens that are present in every cell, the Achilles heel of these highly complex cancers.
“This opens up a way to look at individual patients' tumors and profile all the antigen variations to figure out the best ways for immunotherapy treatments to work, prioritizing antigens present in every tumor cell and identifying the body's immune T cells that recognize them. This is really fascinating, and takes personalized medicine to its absolute limit where each patient would have a unique ... treatment."
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