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Carl June: Forging New Frontiers in Cancer Therapies



June called the rapidly progressing CAR T cell therapy a “disruptive therapy” that has “changed everything” since he first used it to treat a patient seven years ago. | Stephen Waldron/AAAS

Synthetic biology promises to revolutionize cancer care by offering permanent cures to patients with historically untreatable malignancies.

Yet policy and regulation must keep pace with rapidly advancing research to allow new treatments to be made available worldwide, said Carl June during the plenary address at Science Diplomacy 2017, the third annual conference by AAAS’ Center for Science Diplomacy. The conference was held on March 29 at AAAS headquarters in Washington.

June, a professor in immunotherapy at the University of Pennsylvania, described recent triumphs in cancer research that have now been used to treat more than 300 children with leukemia, all of whom remain in remission.

“The idea that we’re working on here is called synthetic biology. We’re making the immune system do things it never could,” said June. “We repurpose cells to become cancer-killers.”

Cancer treatments are evolving rapidly. Unlike conventional chemotherapies and radiation that indiscriminately eradicate fast-growing tissues and ravage people’s bodies with side effects, new therapies specifically target tumors using tailored cells from individual patients.

“It’s a living drug, for the first time,” said June. “It’s unlike anything the pharmaceutical industry has ever done.”

The new treatments, called CAR T cell therapies, eliminate cancer using people’s own cells. Using the immune system to control malignancies has long been a goal for clinicians, but progress was slow because cancer actively suppresses the body’s defense mechanisms.

CAR T cells retrain the immune system to fight cancer. Clinicians extract bone marrow from patients and then genetically engineer the person’s T cells. After reintroducing the modified cells with a transfusion, the newly-trained cancer-killers multiply then seek out and destroy malignancies.

“We take the T cells out, hack the cells, and make them work better,” said June.

The hack that gives CAR T cells their cancer-killing abilities relies on a specially designed surface molecule called a chimeric antigen receptor (CAR) – and hence the technique’s name – which scientists incorporate into T cell genomes using a modified virus. Different CARs determine what types of tumors T cells target. Groups around the world are working to refine all steps of the manufacturing process. 

Research has progressed rapidly since June treated his first patient with CAR T cells in 2010.

“A disruptive therapy that worked in few patients changed everything,” said June.

One of those early patients was a young girl named Emily Whitehead who arrived in June’s clinic, “on death’s door,” with an aggressive form of relapsed childhood leukemia. Now, Emily has remained cancer-free for almost five years and her parents have created a foundation to help other patients access experimental cancer therapies.

Since then, June and other researchers at the University of Pennsylvania, have treated hundreds of people with CAR T cells.

While CAR T cells don’t cause the side-effects associated with chemotherapy and radiation, the new approach is not without risks. Tweaking the immune system to create CAR T cells has caused adverse reactions in some people.

“These are patients that are happy because they are cured from their cancer, but they now have an autoimmune disorder,” said June.

Furthermore, while the approach has shown tremendous promise in treating blood-based cancers like leukemia, solid tumors remain stubbornly difficult to treat with CAR T cells. 

Yet despite setbacks, research continues in hopes of improving the technique further. June speculated that advances in genome editing, such as those enabled by CRISPR/Cas, could add additional modifications to CAR T cells. Such tweaks might allow cells to access the interiors of solid lesions and even prevent autoimmune reactions.

Currently, CAR T cells are being investigated worldwide in more than 380 clinical trials registered at The global nature of CAR T research means that scientists and policymakers need to collaborate to ensure everyone has access to safe and effective treatments.  

“It’s an amazing thing to think that you could do this internationally because it’s a very technologically intensive therapy,” said June. “This is a new and very multidisciplinary industry. It’s so new, it has no standards.”

June is currently working with a consortium of academic and industry researchers, as well as scientists from the National Institute of Standards and Technology to establish sound manufacturing principles for CAR T cells. He predicts that the United States Food and Drug Administration will approve CAR T cell therapies for cancer this year.

Even more applications for cell therapies beyond cancer could become reality in the coming years.

“In the future, it won’t just be cancer, other diseases like Alzheimer’s will be targeted,” said June.

[Associated image: Perelman School of Medicine at the University of Pennsylvania]


Sam Million-Weaver