Jianzhu Chen’s scientific career — which may one day lead to a cancer vaccine — almost never happened. He came of age during the Chinese Cultural Revolution of the 1960s and 1970s that oppressed educated citizens and shuttered academic institutions.
Fortunately, he says, “When I graduated from high school, that was the first year China allowed students to go to university.” After attending Wuhan University, Chen enrolled at Stanford under a then-new program that admitted about 50 Chinese students to U.S. graduate schools.
Today, he is the Cottrell Professor of Immunology and a member of the David H. Koch Institute for Integrative Cancer Research at MIT. His laboratory is painting a clearer picture of how cancer defeats the body’s protections against disease. How? By recreating human tumors and immune responses in mice. While mice that carry functioning human genes, cells, and tissue have existed for decades, Chen has achieved a technological breakthrough in mimicking human biology.
“This might bridge the gap between animal models and human patients,” he says. In other words, testing cancer therapies and vaccines on this new generation of laboratory subjects would help researchers identify only the most promising ones for human clinical trials.
In many cases, our immune cells destroy cancer cells before they turn into a detectable tumor. The immune system also plays a role in rare instances when a developed tumor vanishes without intervention. But, eventually, most tumors trick the immune system into overlooking cancer cells as they multiply and spread.
“We would like to identify how tumor cells suppress the immune response,” says Chen. To do that, he developed a mouse in which prostate tumors occur spontaneously.
“Most people have been studying cancer immunotherapy in transplanted tumors. Unfortunately, this model does not mimic what’s really going on in naturally occurring tumors,” he says. Naturally occurring tumors grow much more slowly than transplanted tumors. That makes them a better environment for studying an anti-tumor immune response, a process that takes weeks.
The immune response in Chen’s prostate-cancer model involves CD8 T cells, a type of white blood cell whose power to target tumors has captivated many cancer researchers. He and his colleagues have observed, for the first time, CD8 T cells infiltrating a prostate tumor and functioning for several days, after which the tumor becomes tolerant to or inactivates them. Aided by this knowledge, the researchers are looking at ways to delay the suppression of CD8 T cells and reactivate those that remain within the tumor.
In a related breakthrough, Chen and colleagues at the Singapore-MIT Alliance for Research and Technology engineered the first strains of mice that produce the full complement of human immune cells. Compared to previous models possessing only a limited number of those cell types, the animals provide a more comprehensive view of the human immune system’s response to a pathogen or vaccine. Chen’s team recently programmed some of these subjects to develop human leukemia and have used them to evaluate potential therapeutics.
Engineering another animal to express several different biological characteristics originating in humans is a technological feat, says Chen. “To develop and optimize all the different components takes time.” But overcoming these challenges, says Chen, “is exciting.”
“We need to use the best models available for human cancer. If we test something and it’s not a success, we can figure out why it’s not working. And that may lead us down the path to something that’s going to work in patients.”