Jenny Shu thought she was ready to leave bench science. After a Ph.D. and two postdoc stints, she had decided she didn’t want to pursue an academic career any further; business development, she thought, was a better fit for her skills and interests. So she earned a master’s degree in finance and interviewed for business jobs, including one at Jounce Therapeutics in Cambridge, Massachusetts, a startup that aims to use the body’s immune system to target cancers. The job she interviewed for was on the business side, but because she had relevant experience from her first postdoc, the position she was offered included both business development and science.
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
Cancer immunotherapy encompasses a broad range of approaches, including the use of antibodies and genetically engineered immune cells, to target cancer cells. The common thread of all these treatments is that they aim to harness the natural protective—and destructive—powers of the immune system to kill cancer. Jounce is one of many startups entering the cancer immunotherapy space; a growing number of large, established pharmaceutical companies have also entered.
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.”
That culture is changing as Jounce grows, Shu acknowledges. “As we get bigger, of course we’re getting more corporate; you just can’t help that. You do have to have a drug at some point,” she says. Consequently, just as in Caruso’s academic lab, leads unlikely to have an impact on treatment may not be pursued. All in all, Shu has found it to be an excellent scientific experience. “I think a startup is a very good transition from academia to industry. You get to wear a lot of different hats, and you get to mold yourself in a way that interests you,” she says.
All together now
Shu is collaborating with researchers at Massachusetts General Hospital and the University of Chicago; the company’s relationships with these institutions are examples of the myriad connections between academia and industry in cancer immunotherapy. Other examples: At the University of Pennsylvania (Penn), researchers are developing a type of engineered T cell for cancer immunotherapy and, in partnership with Novartis, they are establishing the Center for Advanced Cellular Therapeutics on Penn’s campus. In November 2014, Genentech, a member of the Roche group, published three cancer immunotherapy papers in Nature co-authored by academic collaborators at Yale University School of Medicine and Queen Mary University of London, among others. In January 2015, MD Anderson announced a licensing deal with two drug companies for its engineered T cells. Academic researchers at Memorial Sloan Kettering Cancer Center (MSKCC), the National Cancer Institute, the Fred Hutchinson Cancer Research Center, and Baylor College of Medicine are founders or scientific advisers for cancer immunotherapy startups.
“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.
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.”
How to get into cancer immunotherapy
- Don’t be discouraged if your scientific background does not seem ideally suited for cancer immunotherapy work. Researchers enter this field from many different areas, including immunology, cellular biology, and genetics. Startups especially are looking for people with intellectual curiosity and a track record of productivity, which can outweigh experience in this specific discipline, sources say.
- A strong foundation in immunology is highly valued. If you don’t already have this background, consider taking a course, attending immunology lectures, reading the immunology literature, and working in a basic immunology lab.
- Practice collaborating. Cancer immunotherapy is highly interdisciplinary and requires teamwork between basic scientists, translational scientists, physician scientists, and industry. Demonstrating that you can be successful in such collaborative environments will strengthen your career prospects.
- Academics planning their next career steps should take into account the resources available at different institutions. The established centers, such as MSKCC, MD Anderson, and Penn, have facilities that can produce the engineered immune cells required for many cancer immunotherapies. Generating the cells may be more of a challenge at other institutions that are just entering the field.