Chimeric Antigen Receptor Pioneer Sees Solid Tumor Potential

Gina Columbus @ginacolumbusonc
Published: Wednesday, Aug 26, 2015
Carl H. June, MD

Carl H. June, MD

Regarded as a revolutionary advance in combating various hematologic malignancies, chimeric antigen receptor (CAR) gene transfer therapy has exhibited such promise as an anticancer strategy that the approach is likely to be explored across a broad range of solid tumors, according to Carl H. June, MD.

June, who is widely known as a pioneer of this groundbreaking therapy, anticipates that the novel class of agents will improve as research continues, and that the therapies may eventually have wide applications.

“It will be kind of like computer systems, where we are just seeing the launch of Windows 10. What we have right now is CAR 1.0, and I think these therapies are going to get better with the next generations,” June said in an interview with OncologyLive.

“The big question in the field really surrounds solid cancers,” said June. “For example, what will the role of this kind of immunotherapy be with lung cancer? Trials will begin in every solid cancer you can think of by various groups over the next year or so.”

June is the Richard W. Vague Professor in Immunotherapy at the Perelman School of Medicine and director of Translational Research in the Abramson Cancer Center at the University of Pennsylvania. In May, he was honored with the 2015 Giants of Cancer Care award in the Immuno-Oncology category.

June is the leading investigator into CTL019, the world’s first successful and sustained demonstration of the CAR gene transfer therapy as a treatment for patients with leukemia. CTL019 is a form of adoptive immunotherapy in which autologous T-cells are engineered through lentiviral transduction to express a CD19-specific CAR. The autologous T cells are collected through leukapheresis, modified, and then activated ex vivo using anti-CD3/CD28 beads.

In clinical studies, the therapy has demonstrated overall response rates of 90% in adults and children with acute lymphoblastic leukemia (ALL),1 47% in patients with chronic lymphocytic leukemia,2,3 and 68% in individuals with CD19-positive non-Hodgkin lymphomas including diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma.4 The agent also has shown promise in multiple myeloma.5

In July 2014, the FDA granted CTL019 a breakthrough therapy designation as a possible treatment for pediatric and adults patients with relapsed/refractory ALL.

In addition to CTL019, researchers at the University of Pennsylvania are developing CART-meso, in which autologous T cells are modified to target tumor cells expressing the mesothelin protein in patients with advanced solid tumors.6 A pilot study also is ongoing in metastatic pancreatic cancer.7

June shared his thoughts on the evolution and impact of CTL019 and the potential of CAR therapies in an interview with OncologyLive.

OncologyLive: We understand that you have exciting news to share regarding the 5-year survival rate of one of your patients. Can you discuss this?

Dr June: We have worked on making these CAR T cells for about 25 years. However, it was not until July 31, 2010, that our first patient was treated. Now, he has just passed the 5-year landmark and remains free of leukemia, which was his initial form of cancer, and he is enjoying his retirement.

Please describe the therapeutic process using chimeric antigen receptor therapy.

What we do, really, is an ultimate form of personalized medicine. In this case, it starts with a patient’s own immune system. The white blood cells are taken out from the patient’s arm and, in that 5 to 10 day manufacturing process, those cells are then engineered to become leukemia-specific killers, although we can now make them toward other kinds of cancers.

Then, they are given back as a simple blood transfusion to the patient. It is different from all previous therapies in that these are gene-modified. This gene transfer technology makes the cells chimeric. Therefore, they have the properties of other cells but they are not found naturally in the body, so this synthetic biology makes the immune system better than it was to start.

The second unique property is that these cells are living drugs. Our first patient that we mentioned had his infusion 5 years ago, and we still detect these cells in his body. They are hunter cells that are on patrol, and that is the power of the immune system. It can have a memory—in this case, cells that are anti-leukemic maintain the memory—and they have prevented the tumor from coming back.

Could this therapy have an impact in other B-cell and nonhematologic malignancies?

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