Nov 15 2019
A new technique for treating lung cancer by inhaling nanoparticles created at Wake Forest School of Medicine, part of Wake Forest Baptist Health, has been reported by researchers.
As part of the proof-of-concept study, Dawen Zhao, MD, PhD, associate professor of biomedical engineering at Wake Forest School of Medicine, made use of a mouse model to ascertain whether metastatic lung tumors responded to an inhalable nanoparticle-immunotherapy system in combination with the radiation therapy that is usually used for the treatment of lung cancer.
The study has been reported in the current issue of Nature Communications.
The second most common type of cancer is lung cancer, which is also the leading cause of cancer-related deaths among both men and women. More people die due to lung cancer compared to breast, colon, and prostate cancers combined. Immunotherapy looks promising, but at present, it works in less than 20% of patients suffering from lung cancer.
Considerable clinical evidence indicates that during diagnosis, the tumors of a majority of the patients are poorly infiltrated by immune cells. Such a “cold” immune environment in tumors inhibits the immune system of the body from identifying and destroying the tumor cells.
According to Zhao, the ability to overcome such an immunosuppressive tumor environment to work efficiently against the cancer is now an area of keen interest among the scientific community.
Earlier techniques include directly injecting immunomodulators into tumors to improve their immune response. But this technique is usually restricted to surface and tumors that can be easily accessed. Thus, it can be less effective if repeated injections are required to preserve immune response.
The goal of our research was to develop a novel means to convert cold tumors to hot, immune-responsive tumors. We wanted it to be non-invasive without needle injection, able to access multiple lung tumors at a time, and be safe for repeated use. We were hoping that this new approach would boost the body’s immune system to more effectively fight lung cancer.
Dawen Zhao, Associate Professor of Biomedical Engineering, Wake Forest School of Medicine
The nanoparticle-immunotherapy system developed by Zhao and his colleagues administered immunostimulants through inhalation to a mouse model of metastatic lung cancer. When the immunostimulant-loaded nanoparticle was deposited in the air sacs of the lungs, they were absorbed by one particular type of immune cells, known as antigen-presenting cells (APC).
Then cGAMP, an immunostimulant in the nanoparticle, was discharged within the cell, where the APC cell was activated by the stimulation of a specific immune pathway (STING). This is a crucial step in inducing systemic immune response.
The researchers also demonstrated that when the nanoparticle inhalation was combined with radiation applied onto a part of one lung, the result was the regression of tumors in both lungs and prolonged survival of the mice. Moreover, the researchers noted that it thoroughly removed lung tumors in a few of the mice.
The researchers then performed mechanistic studies and showed that the inhalation system transformed the initially cold tumors in both lungs to hot tumors desirable for powerful anti-cancer immunity.
The inhalable immunotherapy developed by Zhao offers various key benefits to earlier techniques—specifically the capability to access deep-rooted lung tumors, since the aerosol that carries the nanoparticulate was designed such that it reaches all portions of the lung—and the viability of repeated treatment by employing a non-irritating aerosol formulation.
It was demonstrated that the treatment was well-tolerated and safe without any adverse immune-related distress in the mice.
The Wake Forest School of Medicine scientists have filed a provisional patent application for their inhalable nanoparticle-immunotherapy system.