Checkpoint inhibitor immunotherapy has revolutionized lung cancer treatment and ushered in a new era of scientific discovery that is focused on empowering our natural immune system to target and eradicate lung cancer. While some patients see a strong long-lasting benefit from checkpoint inhibitor immunotherapy, there remains a significant proportion of patients with advanced non-small cell lung cancer (NSCLC) who do not show a lasting benefit.
Researchers, such as 2019 Career Development Awardee Aaron Lisberg, MD, a medical oncologist at the University of California, Los Angeles, are working to improve outcomes for these patients. LUNGevity Foundation spoke with Dr. Lisberg to learn more about his research approach, the future of immunotherapy, and the impact of the LUNGevity award on his career.
Why is immunotherapy less effective in some patients?
Checkpoint inhibitor immunotherapy is a treatment that takes the brakes off the body’s natural defenses and allows the immune system to target cancer cells. For this type of immunotherapy to be effective, there are two critical steps. First, we need the immune cells to recognize the tumor cells. Second, we need the immune cells to travel to the tumor site and clear the tumor cells. We hypothesize that the reason some patients don’t respond to immunotherapy as well as we would like them to is that one or both of these steps aren’t happening properly. My team and I are working on a treatment that enhances both of these steps to increase the success of immunotherapy in NSCLC.
Describe your research project.
We are conducting a phase 1 clinical trial to study an approach designed to improve immunotherapy outcomes in advanced NSCLC. Eligible NSCLC patients include 1) those whose tumors do not have the EGFR or the ALK alterations and whose cancers have progressed on checkpoint inhibitor immunotherapy or 2) patients whose tumors are EGFR-positive or ALK-positive and whose cancers have progressed on targeted therapy, but have not received an immune checkpoint inhibitor. Historically, both of these patient populations are known to derive less benefit when treated with checkpoint inhibitor immunotherapy.
Our goal is to help reinvigorate the immune response by harvesting healthy cells from the patient’s blood and altering them to overexpress CCL21, a protein known to stimulate the immune response. These modified dendritic cells, key cells involved in activating the immune system, are then injected directly into the patients’ tumors to spur the immune response and recruit additional immune cells to the tumor sites. The patients are also treated with pembrolizumab, a checkpoint inhibitor immunotherapy, to further amplify the effectiveness of the immune response.
How will this research impact patients?
Having a novel approach to re-energize the immune system and stimulate immune activity directly in the tumor itself could significantly improve outcomes for many patients with advanced NSCLC.
When do you expect to have results?
The study should report out in the next couple of years, depending on the pace of patient enrollment. We are concluding the dose-escalation portion of the trial, where we primarily evaluate for patient safety and determine the appropriate dosages for patients. This will be followed by dose expansion where we will treat 12 additional patients at the dose deemed to be safe.
What will be your next steps in the process?
There are a litany of different things that could happen if the results of this trial turn out well. Our first step would be to test it in a larger clinical trial with more patients. We could also consider this approach for treating early-stage disease. Perhaps we will be able to identify a biomarker that will help us select patients who are most likely to benefit from our treatment approach.
Will immunotherapy eventually become personalized, like targeted therapy?
I think immunotherapy treatment may become individualized, but it is more likely to be broken down into lots of little groups. We hope to understand the biological details of each patient’s disease enough to allow us to know which tumors are most likely to respond well to which treatment.
There’s a lot of hard work that needs to be done to get to the next milestone in lung cancer treatment. Trials like ours are very important–they are cutting-edge and backed by solid science. We must carefully design clinical trials to assess a hypothesis and have a strong result that we can learn from. It’ll be an interesting and exciting journey.
How did the Career Development Award from LUNGevity impact your career?
I will always be indebted to LUNGevity for this award. It is the first grant I ever received. I remember when I got the call—I was so happy! It confirmed to me and to my institution that I could become a successful physician scientist. It was an important signal that I was capable of conducting meaningful translational research.
Once I had the LUNGevity award, other funding agencies were willing to take a chance on me. Because of the LUNGevity award, I now have NIH funding, too.
Now I see patients one day a week; the rest of my time has been freed up to follow my passion and focus on lung cancer research.
What do you want to say to people who support lung cancer research?
First and foremost–thank you! You are funding individuals. You are funding the human drive and ingenuity it takes to make a difference in our world. Research is a messy process, but it’s so essential. I think of it like art. If you want beautiful art, you have to support it. And if you want the benefits of advanced science, you have to support it, too.
Looking forward, what are your career goals?
I aim to be an independently funded investigator who sponsors clinical trials and conducts impactful studies. What I like doing the most is developing partnerships and collaborations across scientific disciplines. I love that UCLA offers so many opportunities to work with world-class experts in a variety of different areas. I bring my expertise to the table, they bring their expertise to the table, and we work together to improve outcomes for lung cancer patients and their families.
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Juhi Kunde, MA, is a science writer for LUNGevity.