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Stanford University School of Medicine

Immunotherapy targets identified using new technology

Immune cells spot cancer cells by locating proteins called antigens. Now, researchers have developed a new tool that will help them identify those antigens.

New technology from the bench of Stanford scientists provides a peek at a critical operation of the human immune system: the targeting and killing of cancer cells.

This advancement helps peg exactly what immune cells "see" when they're attacking a tumor cell, according to a Stanford Medicine study, published in Cell.

Like a bomb-sniffing dog scanning an airport for foul play, immune cells patrol the body for antigens -- specific molecules that alert the immune cell to harmful invaders or mutant cells that could cause damage. Only when these cells find an antigen that they bind to, do they deploy an attack, as in the image above, which depicts three T cells preparing to attack a cancer cell. The idea is, if scientists can figure out which antigens the cells latch onto, they can use that information to develop new immunotherapies -- treatments in which the host's immune system is trained to attack harmful cells.

Now, Stanford researcher Christopher Garcia, PhD, has devised a type of test that, in this case, allows specific molecules derived from immune cells to sift through millions of potential antigen matches, and find the correct fit.

From our release:

'The whole foundation of immunotherapy depends on immune cells recognizing specific antigens on tumor cells. That's the basis of the actual killing event -- where the rubber hits the road,' Garcia said. 'But currently we know very few tumor antigens, and there's just been no good way of discovering them.'

Here, Garcia said, is where he sees potential for the new biochemical screen to expedite the identification process... 'This screen is a completely unbiased way of taking a random T cell receptor that's infiltrated a tumor and interrogating it to find out exactly what antigen it is actually seeing,' Garcia said.

Initially, Garcia said he and his colleagues developed the biochemical screen to answer a different, more fundamental question about biology: How do receptors see antigens in the first place?

"I developed the tool to ask that very basic question, not thinking about immunotherapy, or anything like that," said Garcia. "But it was the answer to that question that made us think immediately, 'Okay now we have to go after antigens for tumors of infiltrating T cells."

Ten years later, through the combined power of the new biochemical screen, deep sequencing data and a powerful algorithm, Garcia and his colleagues have been able to single out two antigens targeted by T cell receptors that were previously unknown.

Previously: Previously elusive targets for cancer immunotherapy identified, Successful immunotherapy requires a body-wide response, say Stanford researchers and Corrective braces adjust cell-surface molecules' positions, fix defective activities within cells
Photo by Alex Ritter, Jennifer Lippincott Schwartz and Gillian Griffiths, NIH

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