In a new approach to fighting cancer, scientists from Harvard University have engineered an implantable disc designed to attract immune cells and prep them to attack tumors. Mice with melanoma tumors were much more likely to survive if they'd been implanted with the device, and tumors disappeared in up to half of the vaccinated animals, according to research published today in the journal Science Translational Medicine. Researchers believe that the implant elicits a broader immune response than traditional vaccines, and may therefore prove more effective. A startup called InCytu, based in Lincoln, RI, is now developing the technology for human testing.
Cancer killer: A cross section of a polymer matrix designed to prime the immune system against cancer. Immune cells crawl through the pores and are activated by chemical signals and tumor molecules.A number of vaccines for treating different types of cancer are currently being tested in clinical trials, though none has yet been approved by the U.S. Food and Drug Administration. Unlike traditional vaccines, therapeutic cancer vaccines are designed to halt or reverse the course of the disease after it has developed. Gardasil, Merck's vaccine against the human papillomavirus, is considered a preventative cancer vaccine and acts in a similar way to traditional vaccines. It helps prevent the development of cervical cancer by stopping viral infection--but it cannot treat existing cervical cancer.
While cancer vaccines come in several variations, the general approach is to trigger the immune system to recognize and destroy cells bearing a cancer-specific marker. The immune system can be tuned to cancer cells by injecting patients with specific molecules linked to different types of cancer, or by injecting irradiated cancer cells. Scientists have also tried to enhance this process by training the immune cells in a controlled environment outside the body--the cells are isolated from the patient's blood and exposed to cancer-specific molecules. The primed immune cells are then injected back into the patient, where they travel to the lymph nodes and trigger an immune response against the However, a problem with this approach is that few cells survive the transplant process, making it difficult for the lymph nodes to mount a strong immune response. David Mooney and colleagues at Harvard University have developed an approach that allows this carefully controlled immune training to take place inside the body. A polymer scaffold, made of the same material used in biodegradable sutures and other surgical products, is impregnated with cytokines, signaling molecules produced by the immune system that attract immune cells known as dendritic cells."The cytokines diffuse into the tissue and the [dendritic] cells follow the gradient to the material and crawl right into it," says Mooney.
Vaccine disc: The disc-shaped implant is smaller than a dime. The polymer is also packed with small fragments of genetic material designed to mimic bacterial DNA. These fragments signal to the dendritic cells that a foreign invader is present. Also present are ground-up pieces of the patient's tumor, which show the cells what to attack. The dendritic cells pick up these molecules as they move through the scaffold. The cells then travel to the lymph nodes, where they introduce the target molecules and generate an immune response. "When the implant is in the body, the immune system sees it as dangerous material and attacks it," says Tarek Fahmy, a bioengineer at Yale University who was not involved in the research.
In mice with established melanoma tumors, the vaccine significantly slowed the growth of the tumors and increased animals' survival time. In addition, tumors completely disappeared in 20 to 50 percent of animals given two vaccinations, depending on how long the tumors had been growing. Researchers say this is significant, given that most cancer vaccines considered to be effective in rodents have been shown to prevent formation of tumors rather than to diminish established tumors. However, it's difficult to compare different rodent models of cancer, which can vary widely.
The implant's effectiveness may lie in the immune response that it triggers, says Mooney. It appears to generate the formation of different types of dendritic cells, which may make the immune response more potent. It also appears to dampen a part of the immune system that typically neutralizes the response once it's been activated--maintaining an activated immune system might be important in preventing tumors from recurring. "That is very novel and extremely important for cancer immunotherapy," says Fahmy.
As is often the case with new cancer treatments, it's difficult to predict how well the findings will translate to humans. A number of cancer vaccines have shown success in animal models and then failed in human clinical trials.
By Emily Singer
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