Among the burgeoning success of immunotherapies, adoptive T-cell therapies have stood out. Since Novartis licensed rights to the University of Pennsylvania's CAR-T programs and agreed to help fund the university's Center for Advanced Cellular Therapeutics in August 2012, and data from Penn's and others' anti-CD19 programs emerged in B-cell malignancies, the field has racked up hundreds of millions of dollars in investment. Seattle-based Juno Therapeutics, before going public on 17 November, had already accrued $176 million in a series A and $134 million in a series B round. Kite Pharma in an initial public offering in June 2014 raised $127.5 million (as of Nov. 7 the company was valued at a whopping $1.75 billion by investors). All of this despite the challenges posed by cytokine storm, known clinically as cytokine release syndrome (CRS). “People are coming to realize that T cells can be potent and effective but also quite dangerous, and the need for safety is implicit in this approach,” says Tom Farrell, CEO of Bellicum Pharmaceuticals, a Houston-based company that filed for IPO on 18 November.
CRS develops when the infused T cells proliferate as they attack a tumor, releasing a massive quantity of inflammatory cytokines. Depending on the tumor burden, the cytokine release, whose main actors include interferon-γ and interleukin-6, can cause severe symptoms that can be life threatening. In March, the US Food and Drug Administration placed a trial testing Juno's anti-CD19 therapy at the Memorial Sloan Kettering Cancer Center in New York on temporary hold after two patient deaths. The regulators lifted the hold in August after the investigators amended the trial protocols.
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