‘Groundbreaking’ cancer discovery holds promise for personalized therapy

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We could be one step closer to personalized vaccines; in what has been hailed a “groundbreaking” discovery, researchers suggest it could be possible to encourage the immune system to target and destroy cancer cells by identifying specific antigens on their surface.
[T cells attacking a cancer cell]
Researchers say their findings may open the door to strategies that prime immune cells to target and kill cancer cells.

In the journal Science, an international research team reveals how T cells – white blood cells that help the body fight infection – can recognize antigens that represent genetic faults, or mutations, incancer cells.

Study coauthor Prof. Charles Swanton, of the University College London (UCL) Cancer Institute in the UK, and colleagues say the findings open the door to immunotherapies that could prime these T cells to identify the unique mutations and kill cancer cells.

Immunotherapy for the treatment of cancer – using a patient’s own immune cells to fight the disease – has been increasingly investigated in recent years. Last year, for example, Medical Today reported on two studies that hailed immunotherapy as highly effective against skin and lung cancers.

But there is one major barrier that is preventing the treatment from moving forward: the inability to guide immune cells toward the exact cancer cells they need to kill, while avoiding the destruction of healthy cells.

Identifying cancer targets for immune cells

This latest study may have uncovered much-needed targets on cancer cells, bringing researchers closer to a more precise, effective form of immunotherapy.

Fast facts about cancer

  • There will be approximately 1,685,210 new cancer cases diagnosed in the US this year
  • There are also expected to be around 595,690 deaths from the disease
  • Up to January 1st, 2014, there were more than 14.5 million people alive with a history of cancer in the US.

Learn more about 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,” says study coauthor 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.”

The researchers explain that as a tumor grows, a number of unique mutations arise in various parts of it. These mutations produce antigens on the surface of cancer cells within a tumor, which act as “flags” for T cells, prompting them to launch an attack.

While the T cells have the ability to eradicate all cancer cells within a tumor, they are not always able to reach their goal. The tumor can either launch a defense mechanism that deactivates the immune cells, or there are often simply too many mutations for the T cells to recognize and attack.

“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,” explains Dr. Quezada.

Uncovering the ‘Achilles heel’ of highly complex cancers

For their study, the researchers set out to pinpoint shared and unique antigens that may arise on the surface of cancer cells. To do so, they used The Cancer Genome Atlas (TCGA) to analyze the genetic data of more than 200 patients with one of two different forms of lung cancer – adenocarcinoma and squamous cell carcinoma.

From this data, the team identified certain antigens that represent early genetic mutations that were common across tumor cells.

Moving to the lab, the team isolated T cells from the tumors of two lung cancer patients. They found that their T cells were able to recognize these common antigens, suggesting that tumors contain immune cells that have the ability to identify cancer cells as harmful.

While the T cells were unable to kill the cancer cells due to the defenses the tumors put up, the researchers believe it may be possible to activate the T cells to target all the tumor cells in one go.

For example, a vaccine could be developed that switches on these T cells in a cancer patient, or it may be possible to harvest, grow or administer T cells back into a patient that can identify the common antigens present in each cancer cell.

“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,” says Dr. Quezada.

Prof. Swanton describes the teams findings as “exciting,” adding:

“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, bespoke treatment.”


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