A liquid gel that solidifies upon injection into solid tumors has been developed by researchers, offering a potential treatment for metastatic cancers.
This innovative gel, visible on CT scans, allows for slow-release cancer-fighting treatments, and when combined with immunotherapy, it demonstrated promising results in preclinical models, inducing tumor regression and enhancing survival.
Direct Injection of Cancer Drugs Into Tumors
The Mass General Brigham research team collaborated with the Koch Institute for Integrative Cancer Research to develop a gel delivery system that addresses challenges faced by intratumoral therapy, providing a means to deliver drugs precisely and ensuring a controlled release.
Intratumoral therapy involves the direct injection of cancer drugs into tumors and holds promise for treating solid cancers. However, its success in clinical trials has been limited due to challenges in precise drug delivery and the rapid dissipation of most immunotherapies from the injection site.
The newly developed gel aims to overcome these hurdles, offering an injectable substance that solidifies upon delivery, contains an imaging agent for visibility on CT scans, and can maintain a high concentration of drugs for controlled release.
Avik Som, MD, PhD, of the Department of Radiology at Massachusetts General Hospital, emphasized the gel's innovative approach to intratumoral cancer immunotherapy.
He explained that the gel addresses the issues of visibility and practicality, enabling interventional radiologists to confirm delivery and ensuring that the drug remains in the intended region.
Moreover, the gel, upon injection into a tumor, appears to train the immune system to recognize and attack not only the injected site but also other areas in the body where the same cancer might be present, according to Som.
Testing the Gel
The interdisciplinary research team, comprising engineers and medical professionals, optimized the gel's delivery system in the laboratory, focusing on its chemical structure.
Key considerations included the gel's ability to transition from a liquid state at room temperature for injectability to a solid state at body temperature within the tumor, forming a drug-releasing depot. The gel also needs to retain drug encapsulation and delivery capabilities while incorporating a sufficient imaging agent.
The test of the gel's effectiveness involved treating mouse models of colon and breast cancer, known for their resistance to immunotherapy. The gel delivered imiquimod, an FDA-approved immune-stimulating drug, together with checkpoint inhibitor therapy.
Results showed improved survival rates in both cancer models, with complete regression observed in responders at both the treated and distant tumor sites. For the colon cancer model, 46% of mice survived the combined therapy, and for the breast cancer model, the survival rate was 20%.
Co-corresponding author Giovanni Traverso, MB, PhD, emphasized the significance of inducing responses in distant tumors in challenging-to-treat cancer models.
The researchers are optimistic about moving the technology to clinical applications but acknowledge the need for further safety testing before broader drug efficacy evaluations.
Eric Wehrenberg-Klee, MD, one of the study's first authors, highlighted the potential benefit of treating patients with a single injection, particularly for cancers that are currently challenging to address.
"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," Wehrenberg-Klee said in a press statement.
The findings of the team were published in the journal Advanced Healthcare Materials.
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