Engineered T cells are used as therapy Credit: Cultura RM/Alamy

A cross-country collaboration devoted to adoptive T-cell therapy—considered by some the breakthrough technology of the year—has scored big with investors. In December, Juno Therapeutics of Seattle raised $145 million in a series A round, among the largest biotech A rounds ever assembled. A unique structure teams up three clinicians and researchers from Memorial Sloan-Kettering Cancer Center in New York with three from Seattle's Fred Hutchinson Cancer Research Center and the Seattle Children's Research Institute. Collectively, the group has expertise in both engineered and nonengineered approaches to creating autologous T-cell therapies for cancers. “There was this recognition very early on in the discussions about not just the fact that together it was a strong team, but that the experience that the different groups had was highly complementary,” says Juno CEO Hans Bishop. Investigators from these groups, as well as groups under the direction of Carl June at the University of Pennsylvania and Steven Rosenberg at the US National Institutes of Health, have wowed the cancer field with response rates in B-cell malignancies using genetically-engineered T cells that target CD19. However, CD19 is a “dream target” admits Juno co-founder Stanley Riddell, of the Fred Hutchinson Cancer Research Center, because people can survive the depletion of normal CD19+ B cells. “One of the challenges is to find other such targets,” he says. Although CD19 is expressed on healthy nonmalignant B cells as well as on B-cell tumors, people can survive the killing of normal CD19+ B cells by the chimeric antigen receptor (CAR)-modified T cell. Unfortunately, thus far, few truly tumor-specific surface proteins that can be targeted by CAR T cells have been identified, so in each case one needs to consider the potential toxicity that would result from simultaneous CAR T-cell attack on healthy tissue. Autologous cell therapy, never a darling of investors, has challenges, both logistical and economic, and engineering T cells has some on top of those. “With CAR T cells, you find the patient, they get it once. So you have no recurring revenue, which is a business model issue,” says David Miller of Alpine BioVentures in Seattle. “I think the logistics of that are more difficult than people think,” he says. But with the potential to durably 'cure' patients, the technology is seemingly irresistible. “This is really paradigm shifting. This is taking patients who have advanced refractory malignancies, who have failed everything, and putting them into complete remission,” says Riddell.