New approach paves the way to making dendritic cell vaccines more effective.
Dendritic cells are rare white blood cells that orchestrate the body’s immune defense against tumors or infections. Because they occur rarely in the body, it’s difficult and expensive to isolate them to make vaccines. Instead, scientists have been relying on the one type of dendritic cells they can grow in the lab, even though other types are more effective for fighting cancer.
The authors of the new study set their sights on producing other, more effective types of dendritic cells at scale. They succeeded in doing so with three types of dendritic cells, including one thought to be the best for use in cancer vaccines: cDC1.
“cDC1 are extremely rare in the blood and could not be generated in vitro at large scale. Hence, it has not been possible to isolate or generate high enough numbers of cDC1 to use them,” said Marc Dalod of Centre d’Immunologie de Marseille-Luminy, one of the study’s authors. “By systematically testing different combinations of growth factors and feeder cells, we established an optimal recipe for large scale generation of cDC1.” The results are reinforced by similar findings from another research group.
Now that researchers can produce large numbers of these cells, there’s a lot they’d like to do with them. “The ability to generate large numbers of distinct types of human dendritic cells in vitro is critical for accelerating our understanding of dendritic cell biology and to harness them clinically,” said Nina Bhardwaj of the Icahn School of Medicine, with whom Dalod collaborated on the study.
Once the process is adapted and approved for clinical use, lab-generated cDC1 cells could be used to make and improve dendritic cell vaccines. For example, some vaccines are made by exposing dendritic cells to adjuvants and pieces of tumors in test tubes. When they’re injected into the patient, the dendritic cells are already primed to activate immune cells specific to the corresponding cancer. Lab-generated cDC1 could provide the cells for this type of vaccine.
In another type of dendritic cell vaccine, an adjuvant and pieces of tumor are injected into the patient’s body, delivering them to the patient’s dendritic cells in their natural environment. Lab-produced cDC1 cells could help with this approach too: Researchers can now easily test which combinations of adjuvants and antigens work best with specific cells in the lab. “Functional testing is crucial,” said Dalod. “This protocol will enable performing large scale screenings to determine how to best harness the functions of these cells.”