The novel injectable gel could improve the landscape for intratumoral therapy which has shown limited success in trials.
Intratumoural therapy – when cancer cancerdrugs are injected directly into tumours – is a promising treatment option for solid cancers but has shown limited success in clinical trials.
This is down to an inability to precisely deliver the drug and because most immunotherapies quickly dissipate from the site of injection. But now, a team of researchers has developed a gel delivery system that overcomes these challenges.
Scientists from Mass General Brigham, in collaboration with the Koch Institute for Integrative Cancer Research, have developed a gel that is injectable but solidifies upon delivery. It contains an imaging agent for visualisation under CT scan and can hold a high concentration of drug for slow, controlled release.
The team reports that the gel induced tumour regression and increased survival in mouse models of colon and breast cancer. The treatment also appeared to train the immune system to detect and attack distant tumours that were not directly treated, suggesting that it might be a helpful therapy for metastatic cancers.
The paper was published in Advanced Healthcare Materials.
“This gel tackles the two problems with existing attempts at making intratumoral cancer immunotherapy: making the therapy visible and practical so that interventional radiologists can confirm delivery, and making sure the drug actually stays in the region of interest,” said Avik Som, MD, PhD, of the Department of Radiology at Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system.
“When we inject this gel into a tumour, we’re able to teach the immune system to recognise the cancer and trigger it to attack not only the site where the gel was injected but also other areas in the body where the same cancer may be hiding.”
The research team, which consisted of both engineers and medical professionals, first developed and optimised the gel-delivery system in the lab by tweaking the gel’s chemical structure.
One key aspect of the gel’s design was that it needed to shift from being liquid at room temperature to becoming solid at body temperature inside the tumour, retaining the delivery capability and carrying sufficient imaging agent.
After optimising the gel in the lab, the team tested its ability to treat mouse models of colon and breast cancer that are usually resistant to immunotherapy.
To do this, they used the gel to deliver imiquimod, an FDA-approved immune-stimulating drug, in combination with checkpoint inhibitor therapy. Each mouse had two tumours of the same type, but the researchers only treated one tumour per mouse, which allowed them to test the gel’s ability to stimulate both local and systemic immunity.
They showed that the method improved survival in both cancer models. The treatment resulted in an all-or-nothing response — mice that responded to the treatment showed complete regression of both the treated tumour and a distantly located tumour, while non-responders showed no regression at either site.
For the colon cancer model, 46 per cent (6/13) survived when the checkpoint inhibitor therapy was combined with gel-delivered imiquimod. For the breast cancer model, 20 per cent (3/15) survived when treated with the combined therapies.
“These two tumours remain challenging to treat today, even though immunotherapies are transforming how we think about treatment,” said co-corresponding author Giovanni Traverso, MB, PhD, MBBCH, Department of Medicine at Brigham and Women’s Hospital and an associate professor in the Department of Mechanical Engineering at MIT.
“The fact that we were able to induce responses in distant tumours in these colon and breast cancer models was a big win.”
The researchers are keen to move this technology to the clinic, but it will first need to go through more rounds of testing for safety. They also plan to test its efficacy with a broader panel of drugs.
“This is an early proof of concept, but we’re all actively working together to try and get these technologies to patients,” said Eric Wehrenberg-Klee, MD, assistant radiologist in the Department of Radiology at Massachusetts General Hospital and one of the study’s first authors.
“There’s quite a bit of benefit to be gained by being able to treat patients with a single injection, and we think this technology has the potential to help with cancers that are currently challenging to treat.”
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