The CDI Experts: Binfeng Lu and the Pursuit of Cancer Immunotherapy

Binfeng Lu, Ph.D., an immunologist, has built an accomplished career over two decades: a list of credentials and accomplishments that put him at the forefront of his niche. His work in T cell immunology, and its use in cancer immunotherapies, is helping to blaze a trail into new therapies of the future. He built a highly successful career as a tenured Professor at the University of Pittsburgh.

To more effectively translate his innovative work to the clinic,  he moved his laboratory to the Hackensack Meridian Center for Discovery and Innovation in the fall of 2022. Indeed,  he has found a new home to accelerate his science which could help patients as soon as possible.

“I had a rewarding career at Pitt - but I was still looking for a place to make a bigger impact,” he said. “Our goal is to solve these problems for patients. It’s not purely an academic pursuit.”

Lu and his lab have made huge strides over the last decade into understanding the molecular mechanisms driving cancer immunogenicity and how tumors hijack the body’s natural defenses to better attack. Now his expertise has arrived at the CDI, complementing the work of immunologist colleagues whose work could produce unprecedented breakthroughs.

“Binfeng Lu is an outstanding scientist who strives to move his research insights forward in meaningful ways,” said David Perlin, Ph.D., the chief scientific officer and executive vice president of the CDI. “His work fits well alongside that of fellow senior immunologists Howard Xue and Yi Zhang, which is the foundation of a focus area in T cell biology and immunotherapy at the CDI. This is the way we can accelerate change, and save lives in the future.”

Lu Science
The Lu lab investigates the molecular drivers of tumor immune tolerance and anti-tumor immunity. This foundational look into the tumor immune suppressive microenvironment promises to point toward novel cancer immunotherapies.

Immune suppression is the major driver of cancer development, and a tactic tumors use to beat the immune system, by expressing immune inhibitory molecules and dialing down immune agonists in cancer tissues. But the same tactic in reverse has been seized by scientists in the 21st century, to render cancer cells susceptible to recognition and eradication by T cells - white blood cells of the immune system which play a foundational role in cancer immunotherapy. For more than a decade, Lu has used data science and cutting-edge tumor immunological techniques to study the mechanisms of tumor immune evasion and tumor immune surveillance in animal models and human cancers.

Lu is looking at the immunological approach to cancer holistically, as an overall strategic war against tumor cells. Cytokines - the small proteins used by the immune system - are a focal point, in terms of how they conduct tumor surveillance and what anti-tumor immunity they may bring; these cytokines pose promising immunotherapy candidates in and of themselves, as Lu work has shown. He is also looking at cancer’s actions, including immune-suppression mechanisms in the tumor microenvironment. Yet another thrust is autophagy (the natural process of the body breaking down degraded and abnormal substances) and related amino-acid metabolism in the T cell immune response.

Lu and his colleagues have made significant breakthroughs. They have discovered that epithelial “alarmin” cytokines, such as IL-33 (Interleukin-33) and IL-36, are downregulated during cancer progression - and they showed that delivery of these cytokines to tumor tissues produces potent anti-tumor effects. These studies provide more clues to the theory that tumors downregulate IL-33 and IL-36 as part of their molecular strategy, to dodge the immune system. Considering the evidence, Lu and colleagues have undertaken development of novel cancer immunotherapies, by leveraging the anti-tumor activities of these cytokines. IL-36 armed oncolytic virus has shown great anti-tumor activities in preclinical models and will be tested in clinical trials.

Lu and colleagues have also made great strides in tackling immune antagonist Tim3, an immune checkpoint molecule Lu team first discovered to be uniquely expressed in the regulatory T cells in human cancer tissues.  Lu and colleagues have outlined, in two publications in Nature Nanotechnology and Cell Reports, a gene therapy approach to tackle this pathway as a new approach for cancer therapy.

Taken together, the complex T cell environment could be turned tactically against cancer - and is already being done so effectively, said Lu.

“Not many people realize - some cancers can be cured by immunotherapy,” he said.

SYNERGY at the CDI
“Huge synergy” is developing between the CDI’s labs focused on T cells, said Lu. Each lab is looking at complementary pieces of the T-cell immunology puzzle - and how it could. The lab of Howard Xue, Ph.D., looks inside the cells to better understand at a transcription level what’s happening with T cell memory - and how it could be used in vaccines and cancer therapies of the future. Yi Zhang, M.D., Ph.D., and his laboratory provided early foundations of memory T cells, and continue to discover new ways to treat graft-versus-host  disease (GVHD) and to turn the tide against cancer at a molecular level. In a different but complementary way, Lu and his laboratory are looking at the signals from outside the cells - and how to better promote wanted responses, particularly in cancer.

Already, the cross-pollination between these labs, right under one roof at the CDI, is fostering better science, said Lu.

“In cancer immunology, you have to have a lot of collaborations,” said Lu. “Different people have different sets of know-how.”

Lu said he thinks there are massive strides which could be made in the very-near future - with respect to IL-33 specifically, and in the field of immunology and immunotherapies for cancer, generally.

“There are unanswered questions - we’re at the cutting edge of answering them,” he said.

About Lu
Lu has two children: both grown, and one of whom is a junior at Vanderbilt University. He spends his free time staying physically active, especially by jogging, and also watching sports such as soccer.

His philosophy is about perseverance - and survival through persistence, as he recalls his career arc.

Lu started his career at Tsinghua University in Beijing before coming to Columbia University in New York for his doctorate. He did his postdoctoral work at Yale, where he was prepared extremely well for basic research. But it was the transition to Pitt which was a step toward translational work - making a direct difference from the lab, to a clinical setting.

When he arrived at Pitt as an assistant professor in 2003, he was a well-trained immunologist, but was initially unaware of how his expertise could be applied to cancer. (These were early days in the scientific strategy of using the human immune system itself to fight cancer). But he seized on its promise quickly. It took working with Pitt colleagues which brought him to the burgeoning field of using immunology to combat cancers of all types.

Seeing its promise has spurred his career ever since.

“As a scientist, discovery is key,” he said. “It’s exciting to be part of this work, now, at this time.”