Researchers from Wake Forest University School of Medicine have discovered a potential new way to treat solid tumors by creating new nanoparticles. Cancers with solid tumors include breast, head and neck, and colon cancer.
In the study, Shen Ming, Ph.D., associate professor of cancer biology at Wake Forest University School of Medicine, and his team used nanoparticles to deliver a small molecule called ARL67156to boost anti-tumor immune responses in mouse models colon, head and neck, and metastatic breast cancer, leading to an increased survival rate.
The findings were published in the journal Science Translational Medicine online. Immunotherapy has revolutionized cancer treatment, but only about 20% of patients respond to it.
"Most solid tumors have a poor microenvironment, making them resistant to conventional cancer therapies, including immunotherapy," Meng explained. "But this study shows that nanoparticle therapies are promising."
According to Ming, levels of adenosine triphosphate (ATP), an energy-carrying molecule, are elevated in tumors treated with anticancer therapies and rapidly degraded into adenosine by a series of enzymes that are highly expressed in tumors. The presence of adenosine in tumor microenvironments could contribute to poor therapeutic response.
Compounds such as ARL67156 are unable to enter solid tumors alone due to their poor physical and chemical properties. However, the design of the nanoparticles allows the accumulation and release of ARL67156 selectively in solid tumors.
The researchers used nanoparticles to deliver ARL67156, an enzyme inhibitor that prevents the hydrolysis of ATP to adenosine. Several mouse tumor models have been tested with nanoparticles.
Meng explained, "We discovered that nanomedicine significantly reduced tumor growth and resulted in long-term survival."
Next, the researchers tested how the nanoparticles worked with the anti-PD-1 antibody, common immunotherapy. The researchers note that the treatment works well and synergistically with anti-PD-1 therapy.
Finally, the scientists evaluated nanomedicine in a 3-D model in vitro of tumors from patients with colon or breast cancer. Similar effects have been observed - promoting the death of cancer cells through the anti-cancer immune response.
"Our findings indicate that our nanoparticle therapies could be used to treat human cancers, as well as improve the efficacy of current therapies," Meng said. "These findings warrant further investigation."
Chengqiong Mao, Stacy Yeh, Juan Fu, Mercedes Porosnicu, Alexandra Thomas, Gregory L. Kucera, Konstantinos I. Votanopoulos, Shaomin Tian, Xin Ming. Delivery of an ectonucleotidase inhibitor with ROS-responsive nanoparticles overcomes adenosine-mediated cancer immunosuppression. Science Translational Medicine, 2022; 14 (648) DOI: 10.1126/scitranslmed.abh1261