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their cells. With the upcoming ovarian cancer trial, Brentjens’s cells will have an extra protein—a truncated form of epidermal growth factor receptor, or EGFRt—engineered into them. If something goes wrong, the clinical team can inject patients with an antibody that attaches to the EGFRt and causes the cell to die. “We want to eliminate the T cells in rapid fashion if we see unforeseen toxicity,” says Brentjens.
The EGFRt tag has been incorporated into other Juno CAR-T programs, but there hasn’t yet been the need to activate the kill switch, says Michael Jensen, another of Juno’s scientific founders. Jensen invented EGFRt when he was at City of Hope, a top cancer center near Los Angeles. Now at Seattle Children’s, Jensen says the CAR-T cells in the neuroblastoma trial there have an EGFRt kill switch, as well. They are not armored with cytokines.
It’s all uncharted territory—the latest in a series of frontiers in cancer immunotherapy that researchers, doctors, and patients will continue to push toward as long as the field shows promising results.
Brentjens can’t help but look back at the field’s early days. “Seventeen years ago, ASH”—the American Society of Hematology, which holds a big medical conference every year—“let us present our posters because they felt sorry for us,” he says. “Now here we are, sitting on the edge of our seats for this trial.”
Photo of an armored Czechoslovak Škoda courtesy of Phil DeFer via Creative Commons.