The invention of a unique nanoparticle by Wake Forest University School of Medicine researchers has shown a possible new method of treating solid cancers. Cancers of the breast, head and neck, and colon all have solid tumors.
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Xin Ming, PhD, associate professor of cancer biology at Wake Forest University School of Medicine, and their research colleagues used a nanoparticle to produce a small molecule called ARL67156 to enhance an anti-tumor immune response in mouse models of head, colon, and neck, and metastatic breast cancer, which resulted in increased survival.
The study was published in the journal Science Translational Medicine, which is available online.
Immunotherapy has revolutionized cancer treatment, although only approximately 20% of individuals react to the medicines.
Most solid tumors have a poor microenvironment that can make them unresponsive to conventional cancer therapeutics, including immunotherapy. But this study demonstrates that nanoparticle therapeutics are promising.
Xin Ming, PhD, Associate Professor, Cancer Biology, School of Medicine, Wake Forest University
According to Ming, tumors treated with anti-cancer drugs have high quantities of adenosine triphosphate (ATP), the energy-carrying molecule, which is promptly destroyed into adenosine by a set of enzymes that are abundantly expressed in the tumors. Adenosine in the tumor microenvironment might lead to poor treatment response.
Because of their poor physicochemical qualities, chemicals such as ARL67156 are unable to penetrate solid tumors on their own. The nanoparticle’s design, on the other hand, allows for selective accumulation and release of ARL67156 in solid tumors.
The nanoparticle was employed to deliver ARL67156, an enzyme inhibitor that blocks ATP breakdown into adenosine, in the study. Various mouse tumor models were used to evaluate the nanoparticle.
We found that the nanomedicine substantially suppressed tumor growth and resulted in prolonged survival.
Xin Ming, PhD, Associate Professor, Cancer Biology, School of Medicine, Wake Forest University
The nanoparticle was then put to the test in conjunction with an anti-PD-1 antibody, standard immunotherapy. The treatment performed effectively and synergistically with anti-PD-1 therapy, according to the researchers.
Finally, researchers tested the nanomedicine in a three-dimensional in-vitro model of tumors from colon and breast cancer patients. Enhancement of tumor cell death by anti-cancer immune response was also reported.
Our study suggests there’s potential translation of our nanoparticle therapeutic for treating human cancers and that it might also boost the effectiveness of existing treatments. These findings warrant further evaluation.
Xin Ming, PhD, Associate Professor, Cancer Biology, School of Medicine, Wake Forest University
The research was supported by NIH funds R01CA194064, R21CA267853, and R21CA263759, as well as the National Cancer Institute’s Cancer Center Support Grant P30CA012197 and the National Institutes of Health’s Clinical and Translational Science Award UL1TR001420.
Journal Reference:
Mao, C., et al. (2022) Delivery of an ectonucleotidase inhibitor with ROS-responsive nanoparticles overcomes adenosine-mediated cancer immunosuppression. Science Translational Medicine. doi.org/10.1126/scitranslmed.abh1261.