Identifying Anticancer Immune Cells

A new biosensor can spot potent cancer-killing immune cells.

Scientists have long known that the human immune system has a method for detecting and destroying precancerous cells. But finding the cells behind this defense mechanism in order to study and perhaps even mimic them has proved quite the challenge. Since the malignant precancerous cells are eradicated before we even know they exist, identifying the cells that killed them seemed nearly impossible. Now European researchers have built a microfluidic biosensor that traps single immune cells together with single tumor cells, allowing the researchers to pick the most potent of these cancer killers out of a crowded field.

Cell mates: This microfluidics chip (top) contains 1,536 minute wells, each designed to force contact between two fluorescently labeled cells. An immune cell and a tumor cell are forced into contact inside a single well of a microfluidics chip (bottom). The setup allows researchers to identify, isolate, and study immune cells with particularly potent anticancer characteristics. Credit: COCHISE Project

The project, called Cell On CHIp bioSEnsor (COCHISE), was initiated by microsystems engineer Roberto Guerrieri at the University of Bologna, Italy. Guerrieri noticed that immunologists had no way to identify and isolate those rare immune cells, or lymphocytes, with antitumor properties--only about one in every 1,000 immune cells has such properties.

Together with postdoctoral researcher Massimo Bocchi, Guerrieri created a microfluidics platform with an array of 1,536 microwells. In each well, electric fields force contact between a fluorescently labeled tumor cell and a labeled immune cell. An automated system then scans the array and detects wells in which the tumor cell's color has disappeared, thereby identifying the lymphocytes that are likely most effective against the leukemia and lymphoma cancers they tested.

The researchers then collect the individual cells that have triumphed over the tumor cells andprovide them to immunologists for study and propagation. "Analyzing a cell we know is active is a large step for research, because you can correlate expression of cytokines or gene expression," Bocchi says. "You can then identify genetic properties that are probably responsible for the cell being active against the tumor." He notes that this could one day be used to find new drugs to fight the disease.

Guerrieri and his colleagues are also working to clone entire cell lines from these single, potent lymphocytes. They plan to see if the resulting daughter cells maintain the same anticancer properties. If so, such an approach could be useful for developing cancer vaccines based on a transplant of a patient's own lymphocytes, the researchers say.

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As far as the biosensor is concerned, "the design itself is not really new," says Luke Lee, director of the Biomolecular Nanotechnology Center at the University of California at Berkeley. Others have developed similar designs, although Lee notes that none are as user-friendly as the COCHISE system. Unlike the other devices, Lee says, the biosensor devised by Guerrieri and Bocchi and their collaborators offers a way to cleanly deliver cells to the chip and manipulate them. "Most demonstrations aren't as clean as this," he says.