Researchers at MIT have developed polymer-coated nanoparticles designed to deliver the immune-stimulating molecule IL-12 directly to ovarian tumors, significantly enhancing the effectiveness of immunotherapy in preclinical studies. This innovative approach, when paired with immune checkpoint inhibitors, led to the complete elimination of metastatic tumors in over 80% of treated mice.
While immune checkpoint inhibitors are effective for several cancers, they have shown limited success in treating ovarian cancer due to the tumor”s ability to suppress the immune system. The study, published in Nature Materials, highlights how the delivery of IL-12 can invigorate the immune response against these resilient tumors.
According to Paula Hammond, an MIT Institute Professor and one of the senior authors, the nanoparticles are engineered to release IL-12 directly in the tumor environment, effectively stimulating immune cells to combat cancer. “We have essentially tricked the cancer into stimulating immune cells to arm themselves against that cancer,” she stated.
The research team, which includes Darrell Irvine from the Scripps Research Institute, expressed optimism about the “target-and-release” design of the nanoparticles, which concentrates the cytokine in ovarian cancer lesions and promotes robust antitumor immunity.
The study”s lead author, Ivan Pires, currently a postdoctoral researcher at Brigham and Women”s Hospital, pointed out the challenges posed by the tumor microenvironment (TME) that can hinder T cells, the immune system”s primary cancer-fighting cells, from effectively attacking tumors.
Traditional therapies often fail to activate T cells in ovarian cancer due to the immune-suppressing proteins present. While checkpoint inhibitors aim to remove these suppressive elements, they often do not provide sufficient stimulation to initiate a strong immune response in ovarian cancer patients.
IL-12 has the potential to enhance T cell activity. However, delivering effective doses has been problematic due to side effects associated with systemic delivery, including severe inflammation and toxicity. The new nanoparticle technology allows for localized delivery of IL-12, minimizing these risks while effectively stimulating an immune response.
In earlier studies, the team had developed nanoparticles that could deliver IL-12 but faced issues with rapid release of the cytokine that limited their effectiveness. The latest modifications involve a more stable chemical linker that allows for controlled release over an extended period, enhancing therapeutic efficacy.
In their experiments, the researchers demonstrated that the nanoparticles could successfully target ovarian tumors and gradually release IL-12, leading to a marked increase in T cell recruitment and activation. When used in conjunction with immune checkpoint inhibitors, the results were particularly promising, achieving cure rates exceeding 80% in mouse models.
The researchers also noted the importance of generating immune memory, as evidenced by the ability of cured mice to recognize and eliminate tumor cells upon re-exposure months after treatment. This suggests the potential for long-term protection against cancer recurrence.
The findings underscore the effectiveness of combining tumor-targeting strategies with localized cytokine delivery to enhance immunotherapy outcomes for metastatic ovarian cancer. The team is collaborating with MIT”s Deshpande Center for Technological Innovation to further develop this nanoparticle technology for clinical applications.
