‘Immuno-relay’ chases down hard-to-treat cancers
Racers on a relay team depend on one another to ferry the baton across the finish line. With this concept in mind, University of Illinois Chicago researchers designed a top-of-the-line relay process entirely in the body’s immune system to challenge the ultimate opponent: cancer.
The researchers’ immuno-relay design presents a more efficient, longer-term strategy to eradicate tumors and prevent recurrence. Their work appears in the journal Nature Communications.
Immunotherapy is a cancer treatment that trains your immune system to recognize tumor cells, fight them and prevent them from coming back. It runs on the cancer-immunity cycle, which resembles a relay race: Off with a shotgun start, antigens — or foreign bodies derived from the tumor — trigger the body’s immune response. Next, processing cells take up those antigens and deliver them to the lymph nodes. In the final stretch, the lymph nodes release their anchor: T cells primed to attack the original tumor.
Immunotherapy is promising but limited because tumor sites are hostile to the immune system. Researchers typically conduct the relay’s second leg — the part where antigens bind with processing cells — outside the body, extracting the elements and mixing them before returning them to the patient. The exit and reentry results in inefficiencies like antigen loss and mismatch.
According to the researchers, a way to improve immunotherapy is to engineer the process entirely in vivo — to move the racetrack inside the body.
“This technology can open up opportunities for treating tumors that are unresponsive to therapy — like glioblastoma in the brain — either alone or in combination with existing immunotherapies,” said lead investigator Zongmin Zhao, a UIC professor of pharmaceutical sciences and a member of the University of Illinois Cancer Center.
To do this, the researchers added two players to the relay team: first, a type of processing cell called cDC1s, short for adoptively transferred migratory type 1 conventional dendritic cells; and second, a specially designed antigen-capturing nano-sponge. The nano-sponge helps cDC1s bind with tumor antigens and deliver them to the lymph nodes — all without venturing outside the body.
Their method is called antigen-capturing nanoparticle transformed dendritic cell therapy.
Results indicate that when used in combination with immune checkpoint inhibitors (another variety of immunotherapy), the researchers’ method eliminates colon cancer, melanoma and glioma primary tumors in 50% to 100% of treated mice. In simulations, the method also effectively rejected two potential recurrences of tumors.
“Ours is a promising, broadly effective approach for in situ cancer immunization,” Zhao said. This method can uniquely alter the tumor microenvironment — the cells in and around it — to be less hostile toward the immune system, he added.
Chih-Jia (Bess) Chao, the study’s first author and a doctoral candidate in pharmaceutical sciences at UIC, said next steps for the technology include exploring how the new method can help people.
“Our technology is effective so far, and that makes me very excited,” she said.
Additional UIC co-authors include: Endong Zhang, Duong N. Trinh, Edidiong Udofa, Shan He, Jingtian Zheng, Xiaoying Cai, Qing Bao, Luyu Zhang, Philana Phan, Sara M. Elgendy, Xiangqian Shi, Joanna E. Burdette, Steve Seung-Young Lee, and Yu Gao. Other external co-authors include: Hanchen Lin, Caylee Silvers, Jiawei Huo, and Peng Zhang from Northwestern University.
