Biomedical engineer Jennifer Elisseeff was working on a way to promote healing in trauma patients when a friend of a cancer patient visiting Elisseeff’s lab told her that similar approaches were reported to fight cancer.
A few years later, Elisseeff began research that promised to bridge the fields of immunology and biomedical engineering. She called the emerging field regenerative immunology. It led her to a new use for her trauma-targeted therapy.
Elisseeff works with biologically engineered animal and tumor tissues that are implanted locally at the site of an injury. “The immune system is a first responder when trauma to tissue and cells occur,” says Elisseeff, director of the Translational Tissue Engineering Center. Her engineered biologic materials give it an extra nudge. “They trigger immune cells, particularly T cells, to direct other immune cells to heal the injury,” she says.
Elisseeff and team are collaborating with the U.S. military to study in people, including servicemen and women injured in combat, the safety and activity of her biomaterials. The engineered materials are made in the Kimmel Cancer Center’s GMP facility. If human studies are successful, it creates a framework for eventually transferring the technology to an experimental clinical trial for cancer patients.
The first step was to test the ostensible cancer fighting potential in her laboratory. Elisseeff injected her biomaterials in mice engrafted with human melanoma skin cancer cells, and it hampered the growth of the cancer. “We’ve looked at the lymph nodes near the injection site and lymph nodes in other parts of the body and have identified immune changes directly related to the biomaterials,” she says. These observations indicated that the treatment has the ability to chase down cancer cells that have broken off from the primary tumor and spread to other parts of the body.
Just as important, Elisseeff and team’s findings challenge the common perception that regenerative medicine is cancer promoting. “This has been a nagging concern in our field, but we’ve never actually seen it occur,” she says. “Our research provides evidence that this may not be a concern.”
The promising anticancer activity in animal models occurred using biomaterials alone. Elisseeff says adding immune therapies, such as anti-PD1 blockades, may make it work even better. To find out she is collaborating with cancer immunology experts Drew Pardoll and Jonathan Powell, who have worked with her to establish this fledgling field of regenerative immunology.
Elisseeff met Pardoll when they worked together on Johns Hopkins University President Ronald Daniels’ innovation hub committee aimed at promoting innovation translation to bring life-changing technologies to market. It led to the current collaboration focused on combined biomaterials/immune therapy animal and clinical studies, and Powell is helping decipher the biologic mechanisms. He has provided laboratory models that reveal the specific immune T cells essential to the healing immune response.
“This is the first therapeutic model,” says Elisseeff. “No one has ever before bridged the fields of immune-engineering and regeneration.”
She says they have only begun to scratch the surface of this new type of therapy and admits there is much they need to learn. Still, early findings point to the therapy she has created as a way to heal both wounds and disease. A patient undergoing cancer surgery could have the biologic material injected during the operation to promote healing of the surgical wound and to simultaneously generate a cancer-fighting immune response.
Gene therapy may be an effective treatment option for the deadly brain cancer glioma, but getting the right genes to cancer cells in the brain has proven difficult. Now, for the first time, Johns Hopkins researchers used biodegradable nanoparticles filled with genes to turn an inactive prodrug into a potent brain cancer cell killer. The nanoparticles, encoding a special gene, were injected into brain tumors in rats and followed by treatment with the drug ganciclovir. The treatment successfully killed cancer cells and extended survival in this animal model.
“Our nanoparticles penetrated completely throughout the tumor following a single injection,” says biomedical engineer Jordan Green. “When combined with systematic administration of ganciclovir, rats with malignant glioma lived significantly longer than rats that did not receive treatment.”
Nanoparticles are ultra tiny structures that are about 20 times larger than a molecule but 100 times smaller than a cell, so they can be loaded with genes and small molecules, including immune therapies, and guide and deploy these therapeutics inside cells. These nanoparticles are able to penetrate tumors and deliver immune-system-activating drugs and antibodies that cause immune cells to specifically attack cancer cells. This type of therapy kills cancer cells more effectively and with far few side effects.