CAMBRIDGE, Mass.—David H. Koch, in his remarks at the dedication of the eponymous Institute for Integrative Cancer Research at MIT, decried the proposed cuts in federal spending that would negatively affect ongoing research, his $100 million gift to help fund the institute's new seven-story, 365,000 square-foot facility notwithstanding. Renamed for its benefactor in 2007 as the David H. Koch Institute for Integrative Cancer Research (it had been the MIT Center for Cancer Research since 1974), the institute couples engineers and biological scientists to pursue innovative solutions to myriad medical challenges.
Now, the interdisciplinary team that Koch'sbeneficence helped assemble has designed a new type of nanoparticlethat could safely and effectively deliver vaccines for diseases such asHIV and malaria. Critical components of therapeutic nanoparticlesinclude: a targeting mechanism such as an antibody or aptamer thatidentifies cancer cells by the molecules they express; a destructive mechanism such as a toxin, antibody or RNA interference (RNAi) molecule that disables cancer cells; and molecular packaging such as aliposome or other material that allows the therapeutic agent to traverse the body efficiently.
The new particles, described in the February 20 issue of Nature Materials, consist of concentric fatty spheres that can carry synthetic versionsof proteins normally produced by viruses. These synthetic particleselicit a strong immune response—comparable to that produced by livevirus vaccines—but should be much safer, says Dr. Darrell Irvine, author of the paper and an associate professor of materials science andengineering and biological engineering. The concentric spheres have anextended-release effect that helps produce a stronger response.
Encasing vaccines in liposomes has been tried before in order to help promote Tcell responses but the liposomes have poor stability in blood and bodyfluids. Irvine decided to build on the liposome approach by packagingmany of the droplets together in concentric spheres. Once the liposomesare fused together, adjacent liposome walls are chemically "stapled" toeach other, making the structure more stable and less likely to breakdown too quickly following injection. However, once the nanoparticlesare absorbed by a cell, they degrade quickly, releasing the vaccine andprovoking a T cell response.
In tests with mice, Irvine and hiscolleagues used the nanoparticles to deliver a protein called ovalbumin, an egg-white protein commonly used in immunology studies becausebiochemical tools are available to track the immune response to thismolecule. They found that three immunizations of low doses of thevaccine produced a strong T cell response—after immunization, up to 30 percent of all killer T cells in the mice were specific to the vaccineprotein.
That is one of the strongest T cell responses generated by a protein vaccine, and comparable to strong viral vaccines, butwithout the safety concerns of live viruses, says Irvine. Importantly,the particles also elicit a strong antibody response.
The new particles, described in the February 20 issue of Nature Materials, consist of concentric fatty spheres that can carry synthetic versionsof proteins normally produced by viruses. These synthetic particleselicit a strong immune response—comparable to that produced by livevirus vaccines—but should be much safer, says Dr. Darrell Irvine, author of the paper and an associate professor of materials science andengineering and biological engineering. The concentric spheres have anextended-release effect that helps produce a stronger response.
Encasing vaccines in liposomes has been tried before in order to help promote Tcell responses but the liposomes have poor stability in blood and bodyfluids. Irvine decided to build on the liposome approach by packagingmany of the droplets together in concentric spheres. Once the liposomesare fused together, adjacent liposome walls are chemically "stapled" toeach other, making the structure more stable and less likely to breakdown too quickly following injection. However, once the nanoparticlesare absorbed by a cell, they degrade quickly, releasing the vaccine andprovoking a T cell response.
In tests with mice, Irvine and hiscolleagues used the nanoparticles to deliver a protein called ovalbumin, an egg-white protein commonly used in immunology studies becausebiochemical tools are available to track the immune response to thismolecule. They found that three immunizations of low doses of thevaccine produced a strong T cell response—after immunization, up to 30 percent of all killer T cells in the mice were specific to the vaccineprotein.
That is one of the strongest T cell responses generated by a protein vaccine, and comparable to strong viral vaccines, butwithout the safety concerns of live viruses, says Irvine. Importantly,the particles also elicit a strong antibody response.
Just as some might find the pairing of engineers and biological scientists to be an odd choice, the success of such a combination is also reminiscent of dualities in Koch himself, who while decrying cuts in federal funding for research is also a renowned conservative who sits on the board of the CatoInstitute. He has helped fund the Tea Party movement and was once theLibertarian Party's vice presidential candidate, but he says his dedication tocancer research outstrips his political interests and he urges others to join him in helping compensate for any shortfall in funding from such sources as the National Cancer Institute, other branches of the National Institutes of Health and still other federal agencies.
Robert Urban, executive director of the Koch institute, explains thatits 630 scientists and engineers, now working together in the samefacility for the first time, focus on five key areas of research:nano-based drugs, detection and monitoring, metastasis, personalizedmedicine and cancer immunology.
