A team of clinicians and engineers developed a hydrogel-based controlled-release platform (Imigel) to inject an immunoadjuvant drug to treat cancer in a mouse model. The image-guided therapy turned a “cold” tumor—one that is resistant to immunotherapy—into a “hot” immunotherapy-sensitive tumor, allowing immune cells to target and attack the tumor both locally and systemically.
The findings of Featured Abstract “Image-Guided Intratumoral Cancer Vaccine to Treat Metastatic Immunotherapy Resistant Cancer with and without Cryoablation” will be presented during Sunday’s Scientific Session 1, Ablation 1, 3 p.m. in Room 221AB in the Phoenix Convention Center.
The researchers wanted to figure out a mechanism to inject imiquimod, a topical anticancer medication approved by the U.S. Food and Drug Administration, and get it to stay in the tumor for about 5 days, which is how long it can take to activate the immune system. They also wanted it to be optimized for image guidance.
“The problem with imiquimod is it’s a small molecule, so it disappears very quickly. One of the elements that has been challenging for a lot of our intratumoral injections is what we inject sort of disappears quickly; we don’t have a retention,” said presenting author Avik Som, MD, PhD, an IR resident physician, PGY-5, at Massachusetts General Hospital (MGH).
Working closely with the lab of MGH interventional radiologist Eric Wehrenberg-Klee, MD, engineering collaborators at the Massachusetts Institute of Technology (MIT) developed a radiopaque gel that is liquid at room temperature but solidifies in the tumor in the body.
Using two checkpoint inhibitor (CPI)-resistant metastatic tumor mouse models, researchers evaluated 90-day survival after injection with and without cryoablation. Cryoablation has long demonstrated a rare but exciting immunostimulatory effect, Dr. Som said. The addition of Imigel to systemic CPI significantly increased 90-day survival to 46 percent, compared with CPI alone, at 0 percent.
The addition of Imigel to cryoablation shows an additive effect. Cryoablation further increased the 90-day survival to 58 percent (CPI + Imigel + cryoablation) compared to only a 21 percent 90-day survival with cryoablation and systemic CPI alone. “Imigel thereby enables a more reproducible abscopal effect in previously ‘cold’ tumors, augmenting the IR armamentarium,” Dr. Som said.
“We were actually able to demonstrate that you could get complete regression of a relatively large tumor that we had implanted distal to the site that we treated, which is sort of the dream of a personalized cancer vaccine. In comparison, groups have often been able to show immune stimulation and rejection of microscopic disease, but most patients with metastatic disease have macroscopic tumors that can be resistant to actual regression,” he said. “One of the really exciting things is that we were able to take a clinically approved drug, use materials that are recognized as safe, combine them, and then inject the material with and without cryoablation, and demonstrate that yes, indeed, we can turn a cold tumor hot in many ways just by improving the retention of drugs we already have, suggesting a hopefully faster translation to humans.”
Dr. Som said it was rewarding to partner with the MIT engineers. “A lot of these folks don’t know that interventional radiology exists. When I started this project, they were very heavily focused on how to help surgeons. They were all thinking about [how a surgeon could] cut a person open and you implant the gel into tumor that way. It’s a radical engineering design difference to say, ‘Actually, what if I can get it through a 20-gauge needle? How would you do it?’
“I think a lot of innovation will continue in working with our engineering colleagues, particularly those in advanced material science. IR is a very heavily device-related field focused on how to deliver existing therapies to the right location, and I think applications of biomaterials to focus on what biologics we’re delivering is our next stage.”
