New Technical Service Helps Identify Infusion Reaction Risk

UPDATE: This service is no longer being offered as part of the Technical Service Program, but it is still available through a contractor Cooperative Research and Development Agreement (cCRADA). Learn more about the cCRADA program.

FREDERICK, Md. -- A new technical service offered by the Frederick National Laboratory for Cancer Research will help researchers screen their nanoformulations for the risk of causing infusion reactions. 

Infusions are a common drug administration route for cancer drugs and other treatments, but they can have potentially serious side effects: infusion reactions. These reactions can manifest as fevers, chills, rigors, rashes, chest or back pain, or difficulty breathing. Infusion reactions prevent patients from receiving the appropriate therapeutic dose of the drug, and, in rare instances, they can be fatal.

Infusion reactions are not unique to nanomedicines—they can be caused by traditional medicines, such as biological agents and small molecules. However, they present a significant hurdle for nanomedicines, because of the complex nature of nanoformulations and the nuanced regulatory approval process for these products. Identification of the risk of infusion reactions early in the drug development process could help mitigate potential safety concerns once the product reaches clinical trials.

To help drug developers and patients, the Nanotechnology Characterization Laboratory at the Frederick National Laboratory recently unveiled a new service—a set of three assays (chemical tests) that in combination provide robust data on the potential for a nanoparticle formulation to cause infusion reactions. This service is now available through the Technical Service Program, which offers unique capabilities of the Frederick National Laboratory to external researchers at cost. 

Marina Dobrovolskaia, Ph.D., senior principal scientist and head of the Immunology Section of the Nanotechnology Characterization Laboratory, is the investigator spearheading the new service. Dobrovolskaia is also part of an international working group working to advance the nanomedicine field. The working group recently released a perspective piece in Nature Nanotechnology describing the importance of reliable methods to identify the risk of infusion reactions to move nanomedicines from the bench to the clinic, where they can benefit patients. 

The three NCL assays are among those proposed by the working group, and include complement activation, platelet aggregation, and inflammatory cytokine expression assays. Each assay addresses one of the mechanisms currently known to trigger infusion reactions. Together, they offer a useful and comprehensive package that could help investigators understand the potential risk. 

“These assays are not 100% predictive, but if we see negative results, we can be confident the risk is lower,” said Dobrovolskaia. “We recommend researchers to consider these results in the context of other safety and efficacy data to enable making informed decisions prior to moving a formulation to clinical trials.” She added that relying entirely on animal models may cause researchers to overlook important and dangerous reactions in humans.

Dobrovolskaia also explained that the service could have broader applications. 

“It is intended for researchers who use nanotechnology to formulate drugs and test nanomedicine safety prior to clinical trials,” Dobrovolskaia said. “But it is also helpful to understand immunotoxicity of other (non-nanotechnology) products. The [technical service] mechanism will allow us to serve a broader research community.”

The trio of assays also comes with the unique expertise of the Nanotechnology Characterization Laboratory. The laboratory, which was founded in 2004, recently reached a major milestone: it is currently testing its 400th nanomaterial intended for clinical trials. 

“We’ve tested everything out there in the world of nano, everything except for graphene. The NCL is uniquely positioned in the field in that we have access to different types of nanomaterials and different formulation strategies,” she said. 

Through the new service, the laboratory expects to bring in even more nanoformulations, as well as other drug products, which will help the Nanotechnology Characterization Laboratory continue to expand its expertise and serve as a national resource.