Activate your cancer immunotherapy career

In the new environment, “I just fell back in love with science,” she says. Now she spends all of her time doing science and says that, while there’s a chance she may someday move toward the business side, she’s quite happy. “I’m back to science and I’ve loved it since the day I got here. … My favorite part is being able to, at the end of the day, hopefully go to patients with a drug that will work.”

My favorite part is being able to, at the end of the day, hopefully go to patients with a drug that will work.

A translational focus

Academic researchers aren’t being left out. The field’s first major clinical successes took place in academic labs, some of which, with their intense translational focus, are now acting almost like companies, says Hillary Caruso, a research scientist in the lab of Laurence Cooper at the University of Texas MD Anderson Cancer Center in Houston. “Our lab is kind of akin to an academic biotech startup company,” she says. “The focus is very much on … how we can get [our therapies] into the clinic as quickly and safely as possible.”

This focus has scientific implications. It means, for instance, that interesting research questions about the mechanisms underlying the therapies may sometimes go unanswered if they do not have a direct effect on the treatment. Some academic researchers might find that this is a limiting approach, but Caruso says that this translational focus fits her well. When she started graduate school, she expected to pursue basic research, but “what I’ve come to learn is that translational goals are very near and dear to my heart,” she says. “Right now, I’m getting to work in between excellent scientists and excellent physicians, and I’m trying to marry the two sides. It’s kind of a unique position to be in. … If you are really interested in eradicating diseases and finding new treatments and are focused on clinical applications of what you’re working on, then translational science is very rewarding.”

Shu found similar satisfaction with her work at Jounce. In fact, the company’s translational focus is a big part of what renewed her relationship with science. She likes the applied focus in combination with “really trying to understand the immunology. What is the mechanism and how do we affect the mechanism the best way?” she says. “We care about the science, but we also care a lot about how we can help patients. There’s a really good balance. … It wasn’t too big of a culture shock for me, honestly. It felt like academia for the longest time.”

All together now

“Right now, most of the leaders in this technology who have been around for 5 or 10 years all have significant partnerships with industry,” says Marco Davila, an assistant professor at Vanderbilt University School of Medicine in Nashville. Davila, an M.D.-Ph.D. clinician-scientist, is still establishing his research program—he joined Vanderbilt in January 2014—but he plans to follow the trend and work with industry partners once he is ready for clinical trials. “When I do my first trial, I will have a number of suitors that are ready to partner and share some of those expenses with me,” he says.

Challenges can arise in these types of collaborations, such as deciding who retains ownership of the intellectual property underlying a therapy and how to deal with conflicts that crop up when the goals of industry and the academic partners diverge. Researchers should be careful to establish solid agreements before entering into these types of relationships, these scientists advise. Despite these challenges, Davila emphasizes the benefits that academic researchers can reap by working with industry. “Academia is great for generating novel research and maybe even translating some of it initially into early-stage trials, but there still is a huge financial requirement to do this type of work,” he says. By collaborating with industry partners, “you’re able to get access to financial and structural resources that are less prevalent in academic medical centers, so that’s tremendous. You can … take something from the lab to the clinic that much faster.”

Remaining independent of industry can have advantages, too. Davila notes that he and other junior researchers in his field who have not yet developed industry partnerships have access to opportunities that might not be available to researchers in other fields at a similar career stage. Because he does not have industry relationships that could lead to conflicts of interest—a rarity in cancer immunology—he frequently is asked to review grant proposals and articles, which helps his professional development, he says. This dynamic offers junior researchers “an opportunity to be able to develop into leaders ourselves, in a way that would be harder to do in another field where there’s plenty of senior leaders without conflicts,” he says.

The fundamentals

While many in the field are focusing on translational work, fundamental aspects of immune behavior remain poorly understood. For those who want to stick to the basic research path, exploring these basic elements of the immune system can provide an entry point, as it did for James Allison, one of Jounce’s founders and chair of the MD Anderson immunology department.

Allison pioneered a branch of cancer immunotherapy referred to as “checkpoint inhibitors.” Cancer can elude the immune system by suppressing T cells, which otherwise would attack cancer cells. Checkpoint inhibitors are antibodies that block this suppression, allowing the T-cells to do their intended job. The first of these treatments to be approved by the Food and Drug Administration, ipilimumab, came out of Allison’s lab.

“I didn’t start off saying, ‘I’m going to figure out how to use the immune system to treat cancer,’ ” Allison says. “I tried to figure out what regulated T cells, and once I figured that out I thought, ‘Hmm, I wonder if we can use this to treat cancer?’ The basic science came first.”

“It’s clear that there’s still more to be learned about the basic science,” he continues. “We need people to come in and keep in mind that it’s early days yet and that there’s still a lot of basic science that needs to be done.”

Some industry players also appear to be exploring some of the basic research questions that inform cancer immunotherapy, says Margaret Callahan, a researcher at MSKCC in New York City. She points to the recent Genentech papers as an example. “It’s hard for me to say that [the Genentech work] is a pharma-only question or an academic-only question,” she says. “The divide between the sort of research that’s done in academics and the sort of research that’s done in pharma is not quite as absolute in terms of ‘sides’ as earlier in my career I would have imagined it to be.”

The next generation

Researchers can participate in the cancer immunotherapy boom by pursing a variety of research areas and environments. “There are so many ways to be involved in this area, whether it is as someone who falls on the more clinical side of the spectrum or someone who’s a very, very basic researcher,” Callahan says. “Cancer immunotherapy spans that whole spectrum.”

The future of the therapies remains to be seen. The successes thus far have been notable and the hype has been extreme, but there’s no guarantee that the bubble won’t pop. “It’ll be interesting to see how it settles out,” Callahan says. “Is this going to be a fad and in 5 years everyone’s going to move onto the next thing, and there’ll be a couple of cancer immunotherapy folks left behind? I’m not sure. My feeling is that cancer immunotherapy is here to stay.”

Junior Max Planck researchers win reforms

Elsewhere in Science, 3 April 2015