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Using All Modalities Key to Expanding Immunotherapy Success in Oncology

Laura Panjwani
Published: Monday, Oct 31, 2016

Patrick Hwu, MD

Patrick Hwu, MD

While immunotherapy is currently only beneficial in select cancers, it is possible for this type of treatment to eventually work for all patients, said Patrick Hwu, MD.

“There are potential targets for T cells on almost all cancers,” said Hwu, department chair, Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. “What we need to do is get the T cells activated in the body to recognize those targets, and we will get immunotherapy working in everybody.”

While checkpoint inhibitors may receive the most attention in the immunotherapy space, there are several other ways to manipulate the immune system to fight cancer, including T cell therapy and vaccines. Combinations, including those that pair different types of immunotherapies with each other as well as with targeted therapies, offer the most potential for long-term, durable responses with immunotherapies, said Hwu.

In an interview with OncLive, Hwu discussed the benefits of rational immunotherapy combinations, why some cancers respond better than others to immunotherapy, and why vaccines should not be discounted as effective immunotherapy options.

OncLive: What do you see as the biggest challenge in immunotherapy?

Hwu: I think immunotherapy is eventually going to be useful in all cancers, but right now it’s only working in a subset of cancers, and within those cancers only a certain percentage of patients are responding. The big question is, “How do we get everybody to respond?”

What we do know is that the targets that the T cell recognizes are embedded in a certain molecule, called class 1, on the tumor. They are little peptides that are 9 amino acids approximately, and those targets exist on almost all cancer cells that we’ve looked at.

There are potential targets for T cells on almost all cancers, but how do we get those T cells activated? One way is by adding these checkpoint antibodies; that works in activating the T cells that are already there. The other way is vaccines, and that proliferates the T cells in the body that are already there, and makes more of them to then recognize these antigens. The third way is T-cell therapy, which is when you grow large amounts of T cells outside of the body and give them back. All of these methods work the same way, and that is by a T cell coming in contact with a tumor, and killing that tumor cell. They are all important, and for different cancers, we are going to need different combinations of these approaches.

Do you see potential for combinations with targeted agents and immunotherapies?

What I am most excited about is adding immunotherapy to targeted therapy in a rational way. I think this is going to be very important. But we can’t just put any combination with anything. There are over 300 combinations with PD-1 agents right now, and many of them don’t have a lot of data behind them, so we are subjecting patients to trials without a lot of data, and that is not right.

We need to have much better science behind what to combine together. If we can get the right rational combinations for the right patients, we are going to go a long way toward getting long, durable responses for patients. That is why we are so excited about immunotherapy, because our immune cells can live in the body for a very long time. That is what our patients want; they want their cancer to be controlled not an extra month, but for the long-term.




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Community Practice Connections™: New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of ImmunotherapyAug 13, 20191.5
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