The glow could someday help us use cancer drugs more efficiently.
Experimenting with mice, Johns Hopkins researchers report they have successfully used positron emission tomography (PET) scans to calculate in real time how much of an immunotherapy drug reaches a tumor and what parts of a cancer remain unaffected.
The technique uses PET imaging of a synthesized radiolabeled protein that locks on to tumor cells, letting researchers visually follow where a so-called checkpoint inhibitor drug binds to a tumor as it disperses. “This approach offers a vital step toward directly measuring how well immunotherapy drugs are able to engage a tumor in any given person,” says Sridhar Nimmagadda, Ph.D., associate professor of radiology and radiological science at the Johns Hopkins University School of Medicine and a member of the Sidney Kimmel Comprehensive Cancer Center. If more tests in animals and humans confirm the scan’s precision and safety, its use could streamline cancer therapy by enhancing doctors’ ability to tailor therapy, help determine the therapeutic dose of a drug, and avoid or stop treatments that are not effective, Nimmagadda says.
The study is described in the Feb. 1 issue of The Journal of Clinical Investigation.
Use of checkpoint inhibitors is a type of cancer therapy designed to help the immune system recognize cancer cells as dangerous and target them for destruction. Tumors often hijack these natural protective systems, allowing the tumors to masquerade as healthy tissues. The programmed death ligand 1 (PD-L1) is one such checkpoint target, and it is currently the backbone of immune checkpoint therapies, with three very expensive drugs—atezolizumab, avelumab and durvalumab—now approved by the U.S. Food and Drug Administration (FDA).
However, the Johns Hopkins researchers say, their use is often a shot in the dark, because it’s difficult to predict or quickly track how much PD-L1 is expressed in different tumors and how efficiently those drugs bind to PD-L1 receptors at the tumor in patients.
The research team created a specialized radiolabeled small protein, or peptide, in the lab that binds to PD-L1, which facilitates marking the receptor with a radiotracer that can be seen with PET imaging.
Using their radiolabeled peptide, the researchers investigated whether they could follow the interaction between the drug and the PD-L1 checkpoint protein to measure how thoroughly and quickly the inhibitor drugs bound to this important target in real time.
First, in tests in cells grown in the lab, the researchers confirmed that their radiolabeled peptide would not alter or interfere with the immunotherapy drugs. They said multiple tests showed the radiolabeled peptide bound to PD-L1 with less vigor and could not push off the bound drug. This ability, in theory, would allow the radiolabeled peptide to serve as an efficient marker for PD-L1 proteins still waiting to receive treatment.
They next sought to verify this effect in animals. The researchers treated mice that had implanted human lung tumors with a single dose of atezolizumab—a drug that fights cancer by binding to PD-L1—and waited 24 hours, allowing the checkpoint inhibitor to bind to PD-L1. They followed this treatment with the radiolabeled peptide and PET imaging.
When the mice in the experimental group receiving atezolizumab were compared to controls that received only a saline injection, the researchers found a 77 percent reduction in unoccupied PD-L1 levels in the tumor, indicating that treatment reached many of the PD-L1 proteins.
“The remaining areas indicate parts of the tumor that the immunotherapy didn’t reach,” says Nimmagadda, who is a member of the Institute for Basic Biomedical Sciences at the Johns Hopkins University School of Medicine. “In human patients, this could give us some insight about how to optimize further treatments by increasing the dose or substituting other drugs or therapies more quickly.”
The researchers then tested whether they could use their method to measure changes in PD-L1 receptor levels on a tumor.
Again using mice with human lung tumors, the researchers treated the rodents with a drug that increases PD-L1 levels in tumor cells. This treatment was followed with the radiolabeled peptide. Upon imaging these mice with PET, they found that the radiotracer levels were 65 percent higher than in control animals with normal levels of PD-L1 receptors. These studies showed that changes in PD-L1 levels could be measured without a biopsy during immune checkpoint therapy.
Additionally, in chemical structure studies of the peptide, the researchers found that peptide binding to PD-L1 is similar to each of the immunotherapy drugs the FDA has approved, suggesting that the same performance observed in their experiments would likely translate to treatments with other immune checkpoint drugs.
“These results represent a necessary initial step toward finding safe, effective and personalized doses of immunotherapy,” says Nimmagadda.
The researchers are working on improving the technique, and they plan to begin clinical trials this year.
The Latest on: Immunotherapy
via Google News
The Latest on: Immunotherapy
- Health Kick Podcast: Understanding immunotherapy, why the drug market dried up and Immutep’s profitable potentialon March 22, 2020 at 2:40 am
Stockhead’s resident Health and Biotech expert Tim Boreham is putting down the microscope and picking up the microphone for another instalment ... Read More The post Health Kick Podcast: Understanding ...
- The Role of Immunotherapy on the Survival of Pancreatic Cancer Patientson March 20, 2020 at 2:52 pm
Immunotherapy has revolutionized the treatment landscape of many malignancies, but its therapeutic role in pancreatic cancer (PC) remains unclear. The objective of this study is to investigate the ...
- Global Allergy Treatment Market Report 2020-2025 - Subcutaneous Immunotherapy (SCIT) Expected to Register a High Growth Rateon March 20, 2020 at 5:15 am
/PRNewswire/ -- The "Allergy Treatment Market- Growth, Trends, and Forecast (2020-2025)" report has been added to ResearchAndMarkets.com's offering. The ...
- Assessing the impact of AGS-004, a dendritic cell-based immunotherapy, and vorinostat on persistent HIV-1 Infectionon March 20, 2020 at 3:19 am
Twelve ART-treated, stably aviremic participants were initially enrolled in this step-wise study. Informed consent was obtained from all patients prior to study enrollment. Baseline ART was maintained ...
- Immunotherapy treatment shows promise for some patients with advanced rare cancerson March 19, 2020 at 9:19 pm
Study findings were published in the March 18 online issue of the Journal for ImmunoTherapy of Cancer. The open-label, Phase II study followed 127 patients who had advanced rare cancers: squamous cell ...
- Seattle nonprofit to start immunotherapy trials for coronaviruson March 19, 2020 at 6:40 pm
Corey Casper, CEO of the Infectious Disease Research Institute, said the nonprofit has received funding to begin clinical trials for immunotherapy to combat moderate to severe cases of COVID-19.
- Chi Lin, MD, PhD, on Immunotherapy and Chemoradiation in Pancreatic Canceron March 19, 2020 at 1:24 pm
Immunotherapy can be said to have revolutionized the treatment landscape of various malignancies, but less so in pancreatic cancer. The majority of the initial clinical trials in pancreatic cancer ...
- Cancer Immunotherapy Market 2020 Global Analysis, Opportunities and Forecast to 2025on March 19, 2020 at 3:13 am
New York, March 19, 2020:The cancer immunotherapy marketis expected to grow more than US$ 173 Billion by 2024; Growing at a CAGR of more than 14% in the given forecast period. The report covers ...
- Cancer Immunotherapy Market Size is Projected to Reach US$ 115.4 Billion by 2026on March 19, 2020 at 1:11 am
Cancer Immunotherapy Market (by product type:Monoclonal Antibodies)(by product type:Vaccines)(by product type:Checkpoint Inhibitors)(by product type:Cell Therapies)(by product ...
- How CAR-T Immunotherapy Improves Quality of Life After Cancer Treatmenton March 18, 2020 at 4:03 pm
Share on Pinterest Experts say CAR-T immunotherapy strengthens the body’s immune response to fight cancer, a process that can improve a person’s quality of life after treatment. Getty Images ...
via Bing News