Radiation-immunotherapy strategy shows ‘strong efficacy signal’ in pancreatic cancer
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A novel therapeutic approach that combined radiation and immunotherapy demonstrated the ability to eliminate pancreatic tumors and halt metastases.
A novel variant antibody complex (PD1-IL-2v) combined with radiation may induce a significant systemic memory immune response in pancreatic ductal adenocarcinoma, results of a preclinical study published in Cancer Cell showed.
This response may result in antitumor effect and tumor eradication.
“I want to emphasize that this was done in preclinical models,” Sana Karam, MD, PhD, professor and vice chair of translational research at University of Colorado Anschutz Medical Campus, told Healio. “I’ve been doing pancreatic cancer research for many years, and I’ve never seen anything eradicate tumors like this.”
Karam spoke with Healio about the results so far, the next steps in research and the potential long-term implications for practice.
Healio: What is this new treatment and how does it work?
Karam: This is what we call a novel immunocytokine. It’s a drug engineered with what we call an IL-2 variant. It cannot bind to a certain receptor on cells. That deprives the immunosuppressive cells — the “bad” cells — from using it to divide and grow. At the same time, it can still inhibit T cell exhaustion via PD-1.
The problem with immune checkpoints is that a lot of cells use them. So, this was very carefully designed in terms of biochemical engineering to avoid the immunosuppressive cells while allowing the “good” cells — the cells that recognize the cancer and can kill it — to continue to proliferate or divide.
We also found that in combination with radiation, it causes the good cells to become hyperalert, or polyfunctional. This means they become very vigilant and can multitask, in terms of killing. This T cell polyfunctionality occurs not only in the tumor but also in the blood.
Why is this relevant? Pancreatic cancer tends to be a metastatic disease. The tumor itself is important, but what the tumor drains to — the lymph nodes — is also important. Particularly for a disease notorious for systemic or metastatic spread via the bloodstream, we need to tackle it in the blood.
Healio: Is the first time the two treatments have been combined?
Karam: Yes, and it has worked very well as far as eradication. This means you get rid of the tumor, you reimplant the tumor, and it doesn’t “take.” That tells you that memory is developed with this combination. It’s like a vaccine strategy, where the body develops memory against the cancer so that when you reintroduce it, it doesn’t grow anymore. That is incredibly promising because it tells us that circulating memory cells have developed. Even if a cancer cell were to escape, those T cells are primed and ready.
Healio: What are the next steps for research?
Karam: It’s in phase 1 trials. It’s currently in dose-finding. We are planning on going full-fledged in humans following the models we used in the preclinical stage.
Healio: If this therapy continues to exhibit efficacy, what are the potential implications for practice?
Karam: If it continues to perform well in our studies, this could change clinical practice. The nice thing about the data we saw across multiple tumor models is that not only was there a strong efficacy signal in terms of response and eradication, but we potentially have a biomarker. We can see how the cancer-fighting T cells are doing. The ability of these cells to massively divide and expand and build more soldiers was not minimal. It was a remarkable increase in their ability to proliferate or divide. The best biomarkers are those that are easy to follow and track.
Healio: Is there anything else you feel is important to emphasize?
Karam: Research is the primary way to make any meaningful improvements in patient care. I am immensely grateful to the researchers in my lab for their diligent work, to collaborative industry-academic partnerships and to the Wings of Hope Foundation for supporting so much of our research in pancreatic cancer. I am hopeful that we can soon translate their collective efforts into an effective treatment for patients with pancreatic cancer.
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For more information:
Sana Karam, MD, PhD, can be reached at University of Colorado Anschutz Medical Campus, Research Complex 1 South, 12801 E. 17th Ave., RM L18-4113, Aurora, CO 80045; email: sana.karam@cuanschutz.edu.
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