Yale University scientists have developed a new mechanism for attacking cancerous tumours that intensifies the body’s immune response while simultaneously weakening the tumour’s ability to resist it.
The Yale team developed a new biodegradable nanoparticle that delivers a combination of two very different therapeutic agents to tumour sites, gradually releasing the agents into the tumour vasculature. One agent, a large soluble protein called a cytokine, stimulates the body’s innate immune response. The other, a small-molecule inhibitor, interferes with the tumour’s ability to suppress the immune response. Other drug combinations are possible.
In tests on live mice, the double-loaded particle, called a nanogel, significantly delayed tumour growth and increased survival, the researchers report. They administered the nanogels intravenously and, in separate experiments, directly into the tumours. Further animal tests are planned.
Tarek Fahmy, a bionengineer at Yale and the project’s principal investigator said: ‘We believe this is a paradigm-changing immunotherapeutic method for cancer therapy. In essence, it’s a one-two punch strategy that seems to work well for melanoma and may work even better with other cancers.’
The main challenge facing the researchers was devising a particle that enabled gradual, sustained release of two therapeutic agents with very different properties: the protein, which readily dissolves in the body, and the small-molecule drug, which does not.
The researchers exclusively used components already approved by the US Food and Drug Administration. This could potentially speed up future experiments with other ingredients and human trials, they said.
Their results are reported online in the journal Nature Materials.
Richard Flavell of Yale School of Medicine and the Howard Hughes Medical Institute collaborated on the project. Flavell is also a member of Yale Cancer Center.
The National Institutes of Health; the National Science Foundation; Yale University; the Howard Hughes Medical Institute; and the PEW Charitable Trust provided support for the project.