Having established the effectiveness of her nanoparticle drug-delivery system for cancer immunotherapy, University of Massachusetts Amherst researcher Prabhani Atukorale, has been awarded $2.5 million from the National Institutes of Health to broaden the scope of her vaccine research to include treating those with active cancer.
At the crux of what we're doing, we build what we call 'smarter' medicines."
Prabhani Atukorale, Assistant Professor, Riccio College of Engineering, UMass Amherst
Cancer develops when the immune system fails to communicate with the cell growth it regulates. When these unhealthy cells go unnoticed, tumors grow. Recently, her research has focused on using the nanoparticles in a vaccine to train the immune system to prevent the disease. Now, the research, which will span five years, will adapt them to treat existing cancer by delivering two immune-activating medicines to two distinct locations-the lymph nodes and the tumor itself.
"Last year's paper was all prophylactic, and our results were really exciting, but that kind of lymph node-only approach would not work for a patient who already has an advanced tumor," says Atukorale.
The method she will adapt for cancer treatment is called the prime-pull approach: "We prime the immune response at lymph nodes, and then we pull it to tumors," she explains.
The "pull" is a challenge. In the normal cancer-immunity cycle, the communication between a forming tumor and the nearest lymph nodes eliminates cells that are incorrectly dividing: the unhealthy cells send out signals that the immune system picks up, and in response, the immune system sends out T cells to kill the tumor.
"The problem with immunologically cold tumors is, unlike other types of diseases, tumors hijack the immune system for their advantage," says Atukorale. The tumor is considered "cold" because it creates its own microenvironment to suppress the signals that should attract T cells compared to a "hot" tumor that can be "seen" by the immune system. "Any T cells that are tumor-specific have no chance of finding cold tumors. This is probably responsible for most vaccines that have failed to date."
To ensure that the "primed" T cells are actually "pulled" to the tumor, Atukorale's design will not only be administered to the lymph nodes, but also simultaneously to the tumor.
"In doing so, the particles remodel the tumor microenvironment and now the tumor is no longer hidden for those primed T cells to find their way back in," she says. "By sending the vaccine to both sites, what we're doing is actually completing this crosstalk of the cancer-immunity cycle."
The other strength of Atukorale's work is the nanoparticle delivery system that sends not one but two immune-activating signals. These signals are triggered by compounds called adjuvants.
"Nanoparticles have advantages that free adjuvants do not," she says. Previous research has shown that administering free, unencapsulated adjuvants is not effective at combatting cancer and that adjuvants cannot be combined because, like oil and water, they do not mix. Atukorale's "super adjuvant" nanoparticle can hold two adjuvants, ensuring that both triggers hit the same immune cell at the same time, creating the robust immune response necessary to tackle cancer.
Atukorale's work will start using metastatic melanoma, but she envisions that it could be developed as a platform that could apply to others, such as pancreatic or triple-negative breast cancer.
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