Photo by Aaron Logan
Researchers say they have devised an approach that allows for real-time imaging of the immune system’s response to tumors, without the need for blood draws or biopsies.
The method harnesses PET to identify areas of immune cell activity associated with inflammation or tumor development.
The researchers believe the approach offers a potential breakthrough in diagnostics and the ability to monitor the efficacy of cancer therapies.
The team described their method in PNAS.
Study author Hidde Ploegh, PhD, of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, said that every experimental immunologist wants to monitor an ongoing immune response, but options are limited.
“One can look at blood, but blood is a vehicle of transport for immune cells and is not where immune responses occur,” he said. “Surgical biopsies are invasive and non-random, so, for example, a fine-needle aspirate of a tumor could miss a significant feature of that condition.”
In search of a better monitoring approach, Dr Ploegh and his colleagues leveraged two research tools that have become staples in his lab in recent years.
The first exploits single-domain antibodies known as VHHs, derived from the heavy chain-only antibodies made by the immune systems of animals in the camelid family. Dr Ploegh’s lab immunizes alpacas—his camelid of choice—to generate VHHs specific to immune cells of interest.
The second tool, sortagging, labels the VHHs in a site-specific fashion so that researchers can track the VHHs and their targets in a living animal.
Knowing that the tissue around tumors often contains immune cells such as neutrophils and macrophages, Dr Ploegh and his colleagues hypothesized that appropriately labeled VHHs might allow them to pinpoint tumor locations by finding the tumor-associated immune cells.
Dr Ploegh noted that VHHs’ extremely small size—approximately one-tenth that of conventional antibodies—are likely responsible for their superior tissue penetration and, thus, makes them particularly well suited for such use.
So the researchers generated VHHs that recognize mouse immune cells, then labeled these VHHs with radioisotopes and injected them into tumor-bearing mice. Subsequent PET imaging detected the location of immune cells around the tumor quickly and accurately.
“We were able to image tumors as small as 1 mm in size and within just a few days of their starting to grow,” said Mohammad Rashidian, PhD, a researcher in Dr Ploegh’s lab.
“We’re very excited about this because it’s a powerful approach to pick up inflammation in and around the tumor.”
Drs Rashidian and Ploegh believe that, with further refinement, the method could be used to monitor response to—and perhaps modify—cancer immunotherapy.
“To succeed with immunotherapy, we need more information about the tumor microenvironment,” Dr Rashidian said. “With this method, you could perhaps start immunotherapy and then, a few weeks later, image with VHHs to figure out progress and success of treatment.”
“PET imaging should allow a much more comprehensive look at the entire tumor in its environment,” Dr Ploegh added. “Then we can ask, ‘Did the tumor grow? Did immune cells invade? What has happened to the tumor?’ And to be able to see this without going in invasively is a significant achievement.”
