OCTOBER 02, 2020, NEW YORK – Researchers at the Ludwig Center at Chicago have adapted nanoparticles known as nanoscale metal-organic frameworks (nMOFs) to design a personalized cancer vaccine and demonstrated its potential efficacy in mouse models of colon and pancreatic cancer. Reported in Science Advances, their study describes the construction of nanoparticles that can infiltrate tumors, amplify the effects of radiation and release an immune-stimulating drug to boost the anti-tumor immune responses induced by radiotherapy.
Ludwig Chicago investigator Wenbin Lin and his team have been collaborating with Ludwig Chicago Co-director Ralph Weichselbaum to develop nMOFs with a variety of capabilities for cancer therapy. Designed and constructed in Lin’s laboratory, the nanoparticles are latticed structures that, when irradiated, amplify the generation of free radicals—highly unstable ions that kill cancer cells directly.
For the current study, Lin, Weichselbaum and colleagues examined the anti-tumor effects of an nMOF that is additionally capable of carrying immune-stimulating molecules known as PAMPs. They show that irradiating tumors treated with the nMOFs enhances the killing of cancer cells, releasing cancer antigens and inflammatory molecules that stimulate an anti-tumor immune response by the frontline soldiers of the innate immune system. PAMPs released by the nMOFs further boost that response, which in turn stimulates killer T cells, the primary anti-tumor agents of the adaptive immune response.
The one-two punch of irradiation and PAMP stimulation killed both colon and pancreatic cancer cells with high efficiency, even though these tumor models are resistant to other kinds of immunotherapy. The investigators also show that when combined with checkpoint blockade in the colon cancer mouse model, the anti-cancer immune response it induced extended to distant, untreated tumors as well — working, in other words, like a personalized cancer vaccine.
“By including PAMP delivery with the nMOFs, this is the first time we were able to really enhance the immune response to the antigens,” said Lin, who is also the James Franck Professor of Chemistry at the University of Chicago. “This is entirely different from all of our previous studies because we’ve shown that the nMOFs plus PAMPs can impact all of the aspects required for activating the immune system.”
The researchers are eager to bring the technology to clinical trials, where other versions of the nMOF technology are already being tested, with promising results so far.
“The brilliance of this system is two-fold,” said Weichselbaum, who is also Chair of the Department of Radiation and Cellular Oncology at the University of Chicago. “First, it can improve local tumor control by increasing the killing power of X-rays. Second, while there has been interest in using radiation to stimulate the immune response to fight cancer, it has turned out to be harder than we thought. In this case, the nMOFs are able to activate the innate and adaptive immune systems, which makes this technology very promising for treating cancer in the clinic.”
The news release from which this summary is derived can be found here.