Improving next-generation cancer treatments with cryoimmunotherapy

Northwestern Medicine scientists have developed a more effective method of delivering a cutting-edge cancer treatment, according to findings published in the journal ACS Nano.

During cryoimmunotherapy, immunotherapy drugs are combined with extreme cold to destroy tumor cells. Although the approach has been proven effective, there are drawbacks, said Dong-Hyun Kim, Ph.D., professor of Radiology in the Division of Basic and Translational Radiology Research and senior author of the study.

“Compared to the other ablation methods, cryoablation has reduced pain and recovery time,” said Kim, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “But with cryotherapy, there are some limitations around consistent ice formation inside of the tumor tissue and anti-cancer immune activation.”

In the current study, investigators sought to employ engineered molecular agents called metallic supra-structured cryo-nanocatalysts, or MSCNs, to enhance the effectiveness of cryoimmunotherapy.

First, Kim and his collaborators administered MSCNs in cultured mouse prostate cancer cells. They found that the MSCNs elevated the freezing point of the tissues, enhancing ice formation and anti-cancer immunity responses while also inducing more cell death compared to traditional cryoablation methods.

Next, investigators loaded MSCNs with PD-L1, a protein that jumpstarts antitumor immune responses. The loaded MSCNs were found to eradicate tumors and trigger antitumor immune responses in mouse models of prostate cancer more effectively than traditional PD-L1 injection methods, according to the findings.

Additionally, Kim’s approach increased the activation of CD8⁺ T-cells, fighter cells crucial for targeting and eliminating cancer cells.

The results suggest MSCNs could improve traditional cryoimmunotherapy methods, Kim said.

“When we performed immune characterization and RNA sequencing, it showed that memory T-cells—one of the markers of immune memory—were preventing any kind of additional metastasis of the tumor,” Kim said. “This could be a very promising way to deliver both immunotherapy and local ablation therapy.”

Moving forward, Kim and his collaborators will test the efficacy of MSCNs in additional cancer models, with the ultimate goal of seeking FDA approval.