Combining targeted radionuclide therapy and immunotherapy could improve melanoma survival

June 25, 2018, Society of Nuclear Medicine and Molecular Imaging
PET/CT imaging shows selective and prolonged retention of NM600 labeled with Yttrium-86 -a PET imaging isotope- in tumors while clearing from other normal organs and tissues. Credit: R Hernandez, R Patel, et al., University of Wisconsin-Madison, Madison, Wisc.

Research presented at the 2018 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) shows that combining targeted radionuclide therapy with immunotherapy could improve the survival of patients with metastatic melanoma.

Immunotherapies, which use the patient's immune system to fight disease, have increased the survival of many advanced-stage patients. However, for most patients their cancer will either not respond or initially respond but subsequently become resistant to immunotherapy.

"External beam radiotherapy has been shown to enhance cancer response when used in combination with immunotherapy in preclinical studies," explains Reinier Hernandez, Ph.D., of the University of Wisconsin-Madison. "Results can be significantly limited though in the presence of metastatic disease whereby distant tumors that are not targeted with may be relatively resistant to immune recognition and may even harbor suppressive immune cells that can limit the response of effector cells at the radiated tumor site."

He points out, "The true novelty of our work is that, this is the first time that targeted radionuclide therapy (TRT) has been shown to successfully synergize with immunotherapies. We have demonstrated in our animal model of melanoma that the combination of TRT and immunotherapy not only results in enhanced and durable treatment response but also a high cure rate and establishment of an anti-tumor immune memory."

For the study, a mouse model of melanoma was used. The mice were initially administered yttrium-86 (86Y)-NM600 and had PET/CT scans at 3, 21 and 48 hours post injection to determine the proper activity of yttrium-90 (90Y)-NM600, the TRT agent, that would need to be injected to deliver a desired dose of radiation to the tumor microenvironment(s).

Hernandez explains, "Following intravenous injection of our TRT agent, it undergoes selective tumor uptake and prolonged retention, allowing for the precise delivery of the radiation dose to tumors wherever they are in the body—something that is unique to this form of radiation treatment. We have also demonstrated a low toxicity profile for normal organs and tissues at the low immunomodulatory radiation doses of NM600. Moreover, exposure concerns are minimized because NM600 can achieve this dose in the by delivering a beta-emitter like yttrium-90."

Mice treated with the combination of 90Y-NM600 and anti-CTLA-4 immunotherapy showed tumor regression and improved survival compared to other treatment groups, with 66 percent exhibiting a durable complete response.

Hernandez and key coauthor Ravi Patel, MD, PHD, noted that this study took a multifaceted approach to combined TRT/immunotherapy research, which involved close collaboration with immunology, radiation oncology, dosimetry and imaging researchers at the University of Wisconsin-Madison. Such interdisciplinary collaboration is key to advancing new therapies, and NM600 has potential applications for diverse cancers.

Hernandez points out, "Unlike other receptor targeted TRT agents, whose efficacy is restricted to a limited number of patients, NM600 works through a mechanism that is ubiquitous to almost all cancers. This allows us to expand our combination approach to many other malignancies besides melanoma. We have already shown promising results in preclinical models of breast cancer and neuroblastoma and are currently testing this treatment paradigm in pancreatic and lung cancer models."

Explore further: Older melanoma patients have better response to immune checkpoint blockade therapy

More information: Abstract 119: "Combination of Targeted Radionuclide Therapy and Checkpoint Blockade Augments Therapeutic Response in a Syngeneic Murine Model of Melanoma," Reinier Hernandez, Ph.D., Ravi Patel, Joseph J. Grudzinski, Ph.D., Peter Carlson, Raghava Sriramaneni, Ryan Brown, Bryan Bednarz, Paul Sondel, Zachary Morris, Jamey Weichert, Ph.D., University of Wisconsin-Madison, Madison, WI. SNMMI's 65th Annual Meeting, June 23-26, Philadelphia. jnm.snmjournals.org/content/59 … b0-bb6d-2bceae1a7d35

Related Stories

Older melanoma patients have better response to immune checkpoint blockade therapy

June 13, 2018
Patient age correlates with response to immunotherapy in melanoma and depleting regulatory T cells in young patients may have a therapeutic potential to enhance response in younger patients, according to research from The ...

Researchers find combination can enhance ipilimumab immunotherapy

June 15, 2018
Using a targeted therapy to block a protein that suppresses T cell activity could improve cancer treatment with immune checkpoint inhibitors, researchers at The University of Texas MD Anderson Cancer Center report today in ...

Boosting T cell 'memory' may result in longer-lasting and effective responses for patients

April 16, 2018
Just like people, some T cells have excellent memories. These subtypes known as memory T cells may explain why some immunotherapies are more effective than others and potentially lead to researchers designing more effective ...

Drug combination overcomes barrier to effective melanoma immunotherapy

April 12, 2018
Immunotherapies are treatments that stimulate a patient's immune cells to attack tumors. They can be very effective in melanoma—a common and aggressive form of skin tumor—but nonetheless fail in the majority of patients. ...

Beyond PD-L1: Taking away TIM3 and Tregs stops cancer regrowth after immunotherapy

April 16, 2018
Radiation treatment can boost the effectiveness of anti-cancer immunotherapy. Still, some patients fail to respond to this combination, and while the combination of radiotherapy and immunotherapy is very good at creating ...

Recommended for you

Fusion hybrids: A newly discovered population of tumor cells

September 24, 2018
In a recent study published in Science Advances, Charles E. Gast and co-workers detail the spontaneous process of cancer cell fusion with white blood cells to produce heterogenous hybrid clones in multiple biological systems, ...

Cancer cells evade immunotherapy by hiding telltale marker, suggesting how to stop relapse

September 24, 2018
Harnessing the immune system to treat cancer shows great promise in some patients, but for many, the response does not last long-term. In an effort to find out why, Fred Hutchinson Cancer Research Center scientists are using ...

In zebrafish, a way to find new cancer therapies, targeting tumor modulators

September 21, 2018
The lab of Leonard Zon, MD, at Boston Children's Hospital has long been interested in making blood stem cells in quantity for therapeutic purposes. Looking for a way to test for their presence in zebrafish, their go-to research ...

What can salad dressing tell us about cancer? Think oil and vinegar

September 20, 2018
Researchers led by St. Jude Children's Research Hospital scientists have identified another way the process that causes oil to form droplets in water may contribute to solid tumors, such as prostate and breast cancer. The ...

Novel biomarker found in ovarian cancer patients can predict response to therapy

September 20, 2018
Despite months of aggressive treatment involving surgery and chemotherapy, about 85 percent of women with high-grade wide-spread ovarian cancer will have a recurrence of their disease. This leads to further treatment, but ...

Testing fluorescent tracers used to help surgeons determine edges of breast cancer tumors

September 20, 2018
A team of researchers with members from institutions in The Netherlands and China has conducted a test of fluorescent tracers meant to aid surgeons performing tumor removal in breast cancer patients. In their paper published ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.