Engineered cells detect tiny tumors - C&EN Global Enterprise (ACS

It's a problem that Sanjiv S. Gambhir knows well. The cancer ... Studies in mice suggest this method could spot tiny tumors earlier than existing appr...
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Engineered cells detect tiny tumors The designed immune cells release glowing biomarkers for early cancer detection

detects tumors by sequencing tiny bits of DNA that cancer cells release into the blood. The cell-free DNA approach couldn’t detect tumors until they were then kill it. “It sets the stage for an entirely 1,500–2,000 mm3 in volume. Detecting cancer early is difficult. Imaging approaches, like positron-emission tomog- new area of immunodiagnostics,” he says. Victor E. Velculescu, a cancer biologist To engineer the new cancer-sensing raphy (PET), can’t spot tumors that are who studies cell-free DNA cancer diagsmaller than a few millimeters in diameter, cells, the Stanford team decided to use nostics at the Johns Hopkins University macrophages, since these and blood-based diagnostics struggle with School of Medicine, immune cells naturalparsing the minute quantities of biomarkthinks Gambhir’s aply home in on tumors. ers that signal cancer’s presence from the proach is promising. Next, the lab looked in millions of other molecules in the blood. “It has advantages over the macrophages for To make matters worse, cancer researchexisting methods in genes whose expression ers struggle to find biomarkers that only terms of detecting small levels soared when the cancer cells make. lesions,” he says. immune cells infiltrated It’s a problem that Sanjiv S. Gambhir Eleftherios Diamandis tumors in mice. They knows well. The cancer researcher and and Clare Fiala from the found that expression Radiology Department chair at Stanford University of Toronto levels of one gene, called University School of Medicine has spent agree that the new apArg1, jumped 200-fold the past five years “trying to flip the proach is promising, but in the tumor-homing problem around.” His lab has engineered they also point out that An artist’s rendition of macrophages. The team immune cells to produce glowing protein since the cell sensors macrophages (white cells) took part of the Arg1 gene finding a developing tumor biomarkers when they bump into cancer were tested only in mice, called the promoter—the cells. Studies in mice suggest this method “the conclusions about (black cells) and releasing genetic code that turns could spot tiny tumors earlier than existsensitivity or superiority a glowing, green luciferase ing approaches (Nat. Biotechnol. 2019, DOI: the gene on—and stuck over existing human protein. Blood vessels are it in front of a gene from 10.1038/s41587-019-0064-8). shown in red. cancer diagnostics are all a small crustacean called “This paper is an exciting beginning,” speculation” until tests says Kole Roybal, a cell engineer at the Uni- Gaussia princeps that makes a glowing proare performed in humans. tein called luciferase. versity of California, San Francisco, who is The idea of engineered cell sensors has Since that protein is released from cells, attracted investor interest nonetheless. designing his own disease-sensing cells. But doctors could look for it in the blood or he notes that cell sensors alone may be imGambhir has licensed the technology to a urine of patients to practical. “I think this new San Francisco–based start-up called help diagnose cancer, is unlikely to be viable Earli, which is backed by the tech-focused Gambhir says. Some from a cost perspective venture capital firm Andreessen Horowitz. of the glowing protein unless the cells sense Earli and Andreessen Horowitz both destays inside cells too, and treat the disease.” clined interview requests. meaning a PET scan Gambhir thinks Gambhir’s cancer-sniffing cells aren’t that could be possible —Sanjiv S. Gambhir, Radiology could help doctors dis- perfect yet. They also emit luciferase when in the future. “Right they find a wound in the body because Department chair, Stanford University cover a tumor’s locanow, it seems a bit out School of Medicine tion. The team showed that environment also ramps up Arg1 that the method could there, but if cell theraactivity. But Gambhir stresses that this expies catch on, we can envision a time where detect tumors as small as 25–50 mm3, or periment is a proof of principle. “It is ceryou get an immunization with these cells,” tainly not done and ready for humans,” he about the size of a pencil eraser. he explains. The cells would live in you The scientists compared the engineered says. “I hope it leads to real tools that will forever, detect cancer when it appears, and help people someday.”—RYAN CROSS cells with cell-free DNA screening, which

“It sets the stage for an entirely new area of immunodiagnostics.”

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C&EN | CEN.ACS.ORG | MARCH 25, 2019

C R E D I T: SA N J IV S . GA MB H IR

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