Researchers have developed a liquid gel that solidifies when injected into solid tumors, shows up on CT scans and could slow cancer-fighting treatments. Using the gel in combination with immunotherapy improved survival in mice and affected distant, untreated tumors, suggesting it has potential as a therapy for metastatic cancer.
Injecting anti-cancer drugs directly into tumors – intratumoral therapy – is a promising way to treat solid cancers. However, clinical trials have revealed some shortcomings. One is that most immunotherapies are made of small molecules that are quickly destroyed from the tumor site after injection. The second is imagining in-situ treatments to confirm their on-target delivery.
Now, researchers at Mass General Brigham, in collaboration with the Koch Institute for Integrative Cancer Research, have developed a gel delivery system that overcomes these challenges.
“This gel tackles two problems with current efforts at 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 area of interest,” said Avik Som, said the lead author. Study.
The researchers set out to create a gel that was multifunctional: It had to be injected at room temperature and solidify at the tumor site; It must contain an imaging agent so that the therapy can be visualized using CT imaging; And it had to be able to provide cancer treatment. In this case, the treatment was imiquimod, which is an FDA-approved immune-stimulating drug.
They settled on a co-polymer made of biocompatible poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) in a triblock structure. The triblock structure enabled two important features that enabled the controlled release of imiquimod: first, it self-assembled into micellar nanoparticles that encapsulated the drug, increasing its solubility approximately 2,000-fold and allowing a larger dose. allowed to give; Second, around body temperature, this micellar structure formed a sticky gel. Next, the researchers added iopamidol, a contrast agent, to enable visualization of the intratumoral injection under CT. He named his prison drug delivery system ‘Imigel’.
Using mouse models of colon and breast cancer, which are typically resistant to immunotherapy, researchers gave the animals a single intratumoral injection, a combination of Imigel and checkpoint inhibitor (CPI) therapy. Each mouse had two tumors of the same type, but only one was treated, allowing the researchers to test whether the gel stimulated both local and systemic immunity.
After 90 days of treatment, the combination treatment improved survival in both cancer models. For the colon cancer model, 46% of the mice survived; In breast cancer models, 20% survived. The treatment produced an ‘all or nothing’ response. Mice that responded showed complete regression of the treated tumor and distant tumors, while non-responders showed no regression at any location.
“When we inject this gel into a tumor, we are able to teach the immune system to recognize the cancer and prompt it to attack not only the spot where the gel was injected, but Other areas of the body where similar cancers may also be lurking,” Som said.
The so-called ‘abscopal effect’, where a local therapy produces therapeutic effects in distant metastases, possibly secondary to immune activation, is rarely seen in cancer treatment, especially in cancers that are resistant to CPI therapy. The fact that the combination treatment used in the current study affected distant, untreated tumors has the potential to impact treatments for metastatic cancer.
The researchers will continue to test their gel technology for safety and plan to test its efficacy with other drugs besides imiquimod.
“This is an early proof of concept, but we are all actively working together to bring these technologies to patients,” said Eric Wehrenberg-Clee, one of the study’s co-authors. “There is significant benefit in treating patients with a single injection, and we think this technology has the potential to help cancers that are currently challenging to treat.”
This study was published in the journal advanced health care materials,
Source: Mass General Brigham