loaded with tumor
neoantigens which are unique proteins expressed on the tumor cells
absent from normal cells.
‘Novel nanodisc technology containing the tumor neoantigens releases targeted cancer treatment by activating antigen-specific T cells.’
are basically educating the immune system with these nanodiscs so that immune
cells can attack cancer cells in a personalized manner," said James
Moon, the John Gideon Searle assistant professor of pharmaceutical sciences and
What the Nanodiscs Actually Do
nanodiscs function as a therapeutic vaccine, stimulating antigen-specific
T-cells of the host immune system to fight against and eradicate tumor cells
and prevent further growth of the tumor.
preventive vaccines, which are administered prophylactically, these act as
therapeutic vaccines to target established cancer cells.
idea is that these vaccine nanodiscs will trigger the immune system to fight
the existing cancer cells in a personalized manner," Moon said.
Details and Findings of the Study
research team tried out the nanodisc
technology on mice that had established colon cancers and melanomas
to test its efficacy in preventing
tumor growth and killing cancer cells.
the 'vaccination' with the nanodiscs, it was seen that nearly 27 percent of T-cells in the blood of these mice were active
against the cancer cells.
nanodisc technology was combined with the use of 'immune checkpoint
inhibitors', (another existing form of therapy against cancers), the tumors
were completely eliminated in most of the mice within
the icing on the cake was the finding that when the same mice were injected
again with the same tumor cells after 70 days, their immune system rejected the
tumor cells preventing them from growing, suggesting the presence of immunological memory against the same tumor
suggests the immune system 'remembered' the cancer cells for long-term
immunity," said Rui Kuai, U-M doctoral student in pharmaceutical sciences
and lead author of the study.
holy grail in cancer immunotherapy is to eradicate tumors and prevent future
recurrence without systemic toxicity, and our studies have produced very
promising results in mice," Moon said.
What is Nanodisc Technology
nanodisc is a non-covalent structure composed of a phospholipid bilayer and a
genetically engineered membrane scaffold protein (MSP), which functions akin to
an apolipoprotein A-1.
incorporate a membrane protein target into a nanodisc, the target protein is first dissolved in
detergent, and then mixing it with cholate solubilized phospholipid and MSP
If the detergent is removed, it results in the assembly of the nanodisc
structure around the target protein.
Advantages of Employing Nanodisc
nanodiscs are extremely tiny high
density lipoprotein particles measuring 10 nanometers in diameter
comparison, human hair measures 80,000-100,000 nanometers in diameter.
physical properties of the nanoparticles
(i.e., size, shape, charge, ligand density, and charge) can be modified as
required to facilitate site-specific targeting, fine tuning of
biodistribution, immunogenicity, therapeutic loading and detection by
such as the ones used in this study have been specifically formulated to deliver cancer vaccines to
. There was improved delivery of tumor antigens
loaded onto nanoparticles
that acted as cancer vaccines in
comparison to tumors treated with soluble antigen. This has been demonstrated
in studies showing decreased tumor proliferation following such therapeutic
a powerful vaccine technology that efficiently delivers vaccine components to
the right cells in the right tissues. Better delivery translates to better
T-cell responses and better efficacy," said study co-senior author Anna
Schwendeman, U-M assistant professor of pharmacy.
Following the success of the initial tests on mice, the team of
scientists plan to expand their work to study a larger group of larger animals.