AU researcher teams up to explore cancer drug therapy

On the left is Dr. Yukai He of the Georgia Cancer Center at Augusta University and on the right is Dr. Zihai Li, chair of the Department of Microbiology and Immunology at Medical University of South Carolina. The two are collaborators on CAR T cell therapy research for cancer and spoke Thursday at the Second Southeast Cancer Immunology, Immunotherapy & Inflammation Research Retreat at AU.

Now that a drug therapy for cancer has been approved using the same technique they are seeking to perfect, Dr. Zihai Li and Dr. Yukai He said the excitement in their field is palpable.

 

“It’s very hard to sleep most days,” joked Li, the chair of the Department of Microbiology and Immunology at Medical University of South Carolina, as He of Georgia Cancer Center at Augusta University laughed.

The doctors spoke Thursday at the Second Southeast Cancer Immunology, Immunotherapy & Inflammation Research Retreat at AU about their collaboration, which grew out of a similar conference two years ago.

The approach known as chimeric antigen receptor T cell therapy, or CAR T-cell therapy, involves taking a cancer patient’s killer T cells and engineering a unique molecule on their cell surfaces that can then recognize and attach to a molecule on the cancer cell’s surface, allowing these immune cells to specifically hone in on cancer cells.

The field took a great leap forward last month when the Food and Drug Administration approved a specific CAR T-cell therapy to treat pediatric acute lymphoblastic lymphoma.

In approving the drug treatment now marketed as Kymriah, the FDA hailed it as “historic” as the first gene therapy available to U.S. patients, and FDA Commissioner Scott Gottlieb proclaimed, “We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer.”

The race is on to try and apply the approach to adult cancers and to many other types of cancers – there were 281 clinical trials just in the U.S. seeking to use a CAR T cell approach, with most of them open and looking for patients. The approval of the first therapy only adds to that, Li said.

“The excitement is not just this product, the excitement is the principle,” Li said. “This has now illustrated very loudly and clearly that the immune system is very powerful” and can be used to treat very difficult cancers.

The therapy produces something very different than normal medications because it is a “live drug” that once it is given to a patient can produce cells against the tumor but is also very targeted, He said.

“The antibody has very high specificity so it can guide the T cell to certain places” and produce less toxicity from harming normal tissue, He said.

“Now the question is how do we actually make it more applicable to other types of cancer?” Li said.

He and Li are looking at fundamental questions about the therapy on two main fronts: what type of antigen or target to use for the therapy to attack and what type of T cells should be utilized. For instance, in a study recently published in the journal Cancer Immunology Research, He looked at two types of T cells that could respond to a particular antigen found in liver cancer. One overreacted once it reached the tumor and it was quickly exhausted and died, while another with a lower level of activation could actually proliferate and stayed around longer and was more effective against the tumor cells.

“This is basically training a fighter,” He said. “You want to prepare the solider just right, so when they go to this hostile environment they are ready to fight. So you have to equip your T cell to become specific, and you have to prepare it in a certain way so it can be a better fighter.”

The target is also important and they are studying different antigens and looking for what might be more of a “universal” cell surface protein associated with many cancers, Li said. There are certain types proteins necessary for orderly traffic within normal cells that cancer cells are very reliant upon because of their rapid growth, and there may be “almost cancer-specific expressions” of these proteins, he said.

“We are trying to target this family of proteins,” Li said.

There are still some hurdles to overcome with the therapy. One is it can trigger a very strong immune system overreaction that can make patients very sick, Li said. Another is whether it is going to have a long-lasting effect and be “curative” or if it is a bridge to a curative therapy like a stem cell transplant for certain patients, he said.

“Only time will tell,” Li said. But it is now clear that the game has changed with the approval from the FDA, he said.

“The stamp by FDA really symbolizes that the era of cellular therapy for cancer is here, is upon us,” Li said. “And we better get busy.”

 

Reach Tom Corwin at (706) 823-3213 or tom.corwin@augustachronicle.com

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