Immuno-oncology Driving More Precise Cancer Treatment

Damian McNamara

March 04, 2016

LA JOLLA, California — A new tool that redefines combination therapy for cancer patients could soon be available to physicians.

Epitope-based therapy — giving patients the part of an antigen that will activate and optimize their immune system against their specific tumor — looks so promising that it led to the launch of the Cancer MoonShot 2020 program.

To boost the likelihood of treatment success, doctors would select one or more of these therapies, depending on the genomic characteristics of an individual's cancer, to activate key elements of the patient's immune system.

"We've never had tools to penetrate and get to the new epitope before. We need to go from standard chemotherapy to hand-to-hand combat," said Patrick Soon-Shiong, MD, from the University of California, Los Angeles, who is director of the Cancer MoonShot 2020 initiative. These advances in immunology mean that "oncologists will be virologists, immunologists; it will be a difficult sea change."

Recently, Independence Blue Cross became the first commercial insurer to cover the genomic proteomic sequencing cancer test.

This is not a typical cancer research promise delivered with the caveat that it could take 5, 10, or 20 years to see an impact in day-to-day clinical practice.

Dr Patrick Soon-Shiong

"The day-to-day is now," Dr Soon-Shiong told Medscape Medical News. "We've found many oncologists to participate. We're looking at 60 molecules. We have 20 to 30 trials underway." These studies are already comparing standard of care to standard of care plus immunotherapy, he added.

The goal is not to replace traditional cancer therapies, he pointed out. Instead, "you use all the elements — surgery, chemotherapy, radiation therapy, monoclonal antibodies — based on an informed decision from the genomic proteomic sequencing information," Dr Soon-Shiong explained during a standing-room-only session here at the Future of Genomic Medicine IX.

"The key is cancer is not monomorphic and it cannot be addressed through a single target or with a single therapy," Charles Chiu, MD, PhD, from the University of California, San Francisco, told Medscape Medical News. "You have to attack from many directions, including immunology."

An effective combination approach can also decrease the likelihood of treatment resistance developing over time, a lesson learned in many areas of medicine, including HIV, hepatitis B, hepatitis C, and cancer, he added.

An Era Of Personal Proteomics In Oncology

Oncologists will be virologists, immunologists; it will be a difficult sea change.

This progress could fuel an era of personal proteomics in oncology. Instead of targeting only cancer cells, "you are your cancer, you are the host. We need to treat the host. It's a difficult concept," Dr Soon-Shiong said.

"The protocols will be very exciting because, for the first time, we'll have battlefield awareness; every patient will have complete analysis of a new epitope," he added.

The plan is to perturb the immune system with low-dose chemotherapy and low-dose radiation, and then activate the dendritic cells and the T-cells by giving a subcutaneous injection of an adenovirus, IL-15, or a checkpoint inhibitor. Next, patients will receive a blood transfusion of activated natural killer cells or target natural killer cells to activate the memory T-cells and natural killer cells. "That's the goal," he explained.

A previous limitation of immunotherapy — or what Dr Soon-Shiong calls "immuno-oncology" — has been that only 10% of cancer patients typically have the natural killer cells to help in the fight against cancer. But now researchers have found a way to grow these for the other 90% of us.

"With the memory T-cells and natural killer cells — I'm not going to say cure — but you will get chronic remission with a high patient quality of life. The treatment will literally be outpatient low-dose chemo, two flu shots, three shots, and a blood transfusion," Dr Soon-Shiong said.

How real is this approach? The adenoviral vector "is being quietly developed" in a partnership with the National Cancer Institute. Researchers have identified new epitopes that are about to be filed with the US Food and Drug Administration, he said. In addition, investigators have completed a phase 2 trial of patients with metastatic cancer who failed five lines of chemotherapy. "All they got was this injection, and now they have a median survival of 11 months," he reported.

We've shown we can generate this immunity, and even more exciting, we can generate CD4 cells.

"We've shown we can generate this immunity, and even more exciting, we can generate CD4 cells," he pointed out. Additional trials are underway in colorectal cancer, breast cancer, cancers related to the human papillomavirus, and others.

"No one can accuse you of not thinking big," said Eric Topol, MD, director of the Scripps Translational Research Institute in La Jolla, California, and editor-in-chief of Medscape. "There is a lot of resonance on treating the host. But how do you respond to naysayers?"

"Our hypothesis is that your immune system is your biggest protector," Dr Soon-Shiong explained. He noted that the initial success of the preclinical trials serves as proof of concept. In terms of adverse effects, "we have the most experience with the adenovirus vector, and happily we've seen very minimal side effects — one hypoglycemic event from tumor cell lysis. We've treated 50 patients with no serious adverse events," he reported.

The Cancer MoonShot 2020 execution plan lays out the steps required to bring all this to fruition. Each of the 10 milestones, some already completed, are tied to specific dates. When asked if this was to keep everyone accountable and on schedule, Dr Soon-Shiong replied, "Yes, including me."

He called on physicians and researchers to help move the oncology field toward personalized proteomics. "I'm initiating this, but everyone has to take responsibility to collaborate," he said. "Cancer care is local; 80% of care is in the community setting. We want to support community oncologists and move academic medical centers to be more collaborative with community oncologists."

And "we want physicians to refer patients to our trials," he said.

Dr Soon-Shiong is founder of NantWorks and Nanthealth. Dr Topol is editor-in-chief of Medscape and host of Medscape One-on-One, in which he converses with the most interesting people influencing medicine. Dr Chiu has disclosed no relevant financial relationships.

Future of Genomic Medicine (FOGM) IX. Presented March 3, 2016.


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