Using a hydrogel to deliver immunotherapy drugs directly into a tumor improved treatment of immune-resistant malignancies.
The findings of “Development and preclinical evaluation of an immunotherapy-eluting hydrogel platform for stimulating tumor immunity”—which was selected as an SIR Abstract of the Year—will be presented at 10:30 a.m. as part of Wednesday’s Closing Plenary, Hall 6 in the Phoenix Convention Center.
Immunotherapy has revolutionized treatment for many different types of cancers—when it works. “For the majority of patients it doesn’t have a beneficial effect. For the ones who it does work for, it can have quite astonishing and amazing results,” said presenting author Rahul Sheth, MD, associate professor in the department of interventional radiology at MD Anderson Cancer Center.
At MD Anderson, Dr. Sheth and colleagues are studying ways to manipulate tumors to make them more sensitive to immunotherapy. One of the challenges with immunotherapy is getting the immunomodulatory drug to stay inside the tumor. “It’s like injecting a syringe into an apple: Most of it is going to spill out; it’s not going to stay inside the apple,” Dr. Sheth said.
With that in mind, the team began looking at biomaterials that could soak up the medication and potentially distribute it over a prolonged period.
The research team applied a gellan-based hydrogel, called ImmunoGel, and used it to deliver two formulations into mice injected with B16 melanoma and MC38 colorectal cancer, two cancers typically resistant to immunotherapy. One injection was filled with the immunostimulatory cytokine interleukin-12 (IL-12), while the other had a small-molecule CD40 agonist, which can induce anticancer T cell response.
The gel arms were compared to mice that had blank hydrogel injections or saline injections. The team harvested the tumors seven days after implantation and performed immune profiling using immunohistochemistry, flow cytometry, single-cell RNA sequencing and spatial proteomics.
ImmunoGel with IL12 resulted in a significant increase in effector T cells for both treated and nontreated tumors in both the melanoma and colorectal cancer models. The gel with CD40 agonist increased CD8+ cell populations within the treated and untreated tumors and resulted in suppressed tumor growth compared to the sham injections.
Ongoing preclinical work includes finetuning drug delivery and investigating the best combinations with systemic therapies.
“We in IR can play a big role in the overall field of immunotherapy for cancer by taking these concepts that are very intuitive to us, in the sense that you have to deliver the therapy where it’s supposed to go, and that we can use different techniques and different materials to improve that delivery,” Dr. Sheth said. “The ultimate outcome is a very big, ambitious, but achievable, goal, which is expanding the efficacy of immunotherapy across the cancer spectrum. IR has this opportunity and potential to really make a big impact on cancer immunotherapy.”
