A first-of-its-kind nanoparticle vaccine immunotherapy that targets several different cancer types has been developed by researchers at the University of Texas Southwestern Medical Center.
The nanovaccine is made up of tumor antigens - tumor proteins that can be recognized by the immune system - within a synthetic polymer nanoparticle. Nanoparticle vaccines deliver minuscule particulates that stimulate the immune system to mount an immune response, with the goal to help people’s own bodies fight cancer.
Dr. Jinming Gao, Professor of Pharmacology and Otolaryngology at UT, said:
“What is unique about our design is the simplicity of the single-polymer composition that can precisely deliver tumor antigens to immune cells while stimulating innate immunity. These actions result in safe and robust production of tumor-specific T cells that kill cancer cells."
Nanoparticle Vaccine Activation
Typical vaccines require immune cells to pick up tumor antigens in a “depot system” and then travel to the lymphoid organs for T cell activation, Dr. Gao said. Instead, nanoparticle vaccines can travel directly to the body’s lymph nodes to activate tumor-specific immune responses.
The research was a collaboration between the laboratories of study senior authors Dr. Gao and Dr. Zhijian “James” Chen, Professor of Molecular Biology and Director of the Center for Inflammation Research.
“For nanoparticle vaccines to work, they must deliver antigens to proper cellular compartments within specialized immune cells called antigen-presenting cells and stimulate innate immunity. Our nanovaccine did all of those things,"
said Dr. Chen, also a Howard Hughes Medical Institute Investigator and holder of the George L. MacGregor Distinguished Chair in Biomedical Science. In this case, the experimental UTSW nanovaccine works by activating an adaptor protein called STING (STimulator of INterferon Genes), which in turn stimulates the body’s immune defense system to ward off cancer.
Polymeric Drug Delivery
The scientists examined a variety of tumor models in mice: melanoma, colorectal cancer, and HPV-related cancers of the cervix, head, neck, and anogenital regions. In most cases, the nanovaccine slowed tumor growth and extended the animals' lives.
Other vaccine technologies have been used in cancer immunotherapy.
However, they are usually complex - consisting of live bacteria or multiplex biological stimulants, Dr. Gao said. This complexity can make production costly and, in some cases, lead to immune-related toxicities in patients.
With the emergence of new nanotechnology tools and increased understanding of polymeric drug delivery, Dr. Gao said, the field of nanoparticle vaccines has grown and attracted intense interest from academia and industry in the past decade.
“Recent advances in understanding innate and adaptive immunity have also led to more collaborations between immunologists and nanotechnologists,” said Dr. Chen. “These partnerships are critical in propelling the rapid development of new generations of nanovaccines."
The investigative team is now working with physicians at UT Southwestern to explore clinical testing of the STING-activating nanovaccines for a variety of cancer indications. Combining nanovaccines with radiation or other immunotherapy strategies such as “checkpoint inhibition” can further augment their anti-tumor effectiveness.
Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen, Matthew R. Porembka, Jayanthi Lea, Arthur E. Frankel, Yang-Xin Fu, Zhijian J. Chen & Jinming Gao A STING-activating nanovaccine for cancer immunotherapy Nature Nanotechnology (2017) doi:10.1038/nnano.2017.52
Image: UT Southwestern