Nicole Steinmetz, the George J. Picha Designated Professor in Biomaterials, received a major grant from the National Institutes of Health to help understand how a virus-like particle from plants stimulates potent anti-tumor responses.
The new U01 award, totaling nearly $3 million, is provided by the National Cancer Institute. For the funded study, Steinmetz is teamed up with Steve Fiering, professor of microbiology and immunology at Geisel Medical School at Dartmouth College. They will also collaborate with Julian Kim and Sourabh Shukla, members of the Case Comprehensive Cancer Center, as well as P. Jack Hoopes, a veterinarian and cancer researcher at Geisel.
Under the grant, Steinmetz and colleagues will further test a tiny nanoparticle-based therapeutic that her team developed, which targets the body’s own cancer immunity cycle. The therapeutic, derived from a virus-like particle from plants, is about 30 nanometers in diameter; in comparison, a human hair is about 75,000 nanometers in diameter.
Researchers have long known that a person’s immune system has the potential to recognize and destroy tumor cells. With tumor growth, cancer cells release substances known as tumor-associated antigens into the blood stream. These antigens have a unique molecular “zip code” that is recognized by specific immune cells called antigen-presenting cells, also circulating in the blood on “patrol.” The antigen-presenting cells capture the tumor-associated antigens and transport them to another class of specialized immune cells known as cytotoxic T lymphocytes. The antigen-presenting cells “train” the cytotoxic T lymphocytes (killer T cells) to recognize and kill the tumor cells using the tumor-associated antigens. Traveling through the blood stream, the activated killer T cells, in turn, recognize the cancer cells (based on the tumor-associated antigen training) and proceed to kill the cancer cells. During this last step, additional tumor-associated antigens are released and the cycle repeats itself.
But as a tumor progresses, it may respond to the body’s natural immunity system by activating immune-suppressive mechanisms, essentially turning off the body’s own cancer-defense mechanisms. Conversely, the Steinmetz immunotherapy strategy can “flip the switch” by turning off the immune-suppressive environment and turning on the cancer immunity cycle to elicit a potent immune response against the tumor.
Data by Steinmetz and Fiering (Nature Nanotechnology, 2016) show that the proposed nanoparticle cancer immunotherapy generates a highly potent anti-tumor immunity response even in cancers such as melanomas, which are resistant to attack by the immune system. In addition to melanoma, the proposed therapy exhibits clear treatment efficacy and similar anti-tumor immunity performance in metastatic ovarian and metastatic breast tumor models.
