Good news! Cancer is history (soon)! This new therapy attacks metastatic tumors and has memory to prevent recurrence!
"... To elicit a better response, MIT researchers have designed new nanoparticles that can deliver an immune-stimulating molecule called IL-12 directly to ovarian tumors. When given along with immunotherapy drugs called checkpoint inhibitors, IL-12 helps the immune system launch an attack on cancer cells.
Studying a mouse model of ovarian cancer, the researchers showed that this combination treatment could eliminate metastatic tumors in more than 80 percent of the mice. When the mice were later injected with more cancer cells, to simulate tumor recurrence, their immune cells remembered the tumor proteins and cleared them again. ...
In the new study, the researchers modified the particles so that IL-12 would be released more gradually, over about a week. They achieved this by using a different chemical linker to attach IL-12 to the particles. ...
To make sure that the particles get to the right place, the researchers coat them with a layer of a polymer called poly-L-glutamate (PLE), which helps them directly target ovarian tumor cells. Once they reach the tumors, the particles bind to the cancer cell surfaces, where they gradually release their payload and activate nearby T cells. ..."
From the abstract:
"Immunotherapies such as immune checkpoint inhibitors are effective in treating several advanced cancers, but these treatments have had limited success in metastatic ovarian cancer.
Here we engineered liposomal nanoparticles carrying a poly-ʟ-arginine/poly-ʟ-glutamate coating that promotes their binding and retention on the surface of ovarian cancer cells. Covalent anchoring of the potent immunostimulatory cytokine interleukin-12 (IL-12) to phospholipid head groups of the liposome core enabled the polymer-coated particles to concentrate IL-12 in disseminated ovarian cancer tumours following intraperitoneal administration. Shedding of the layer-by-layer coating and serum-protein-mediated extraction of IL-12-conjugated lipids from the liposomal core over time enabled IL-12 to disseminate in the tumour bed following rapid nanoparticle localization in tumour nodules.
Optimized IL-12-polymer-coated nanoparticles promoted robust T cell accumulation in ascites and tumours in mouse models, extending survival compared with free IL-12 and sensitizing tumours to immune checkpoint inhibitors, eliciting strong immune responses and immune memory.
Overall, these findings support the potential of these polymer-coated nanoparticles for the sustained delivery of IL-12 to disseminated metastatic ovarian cancer."
Fig. 3: Mal LbL NPs efficiently target and deliver IL-12 to OC tumour nodules.
No comments:
Post a Comment