One avenue researchers have begun exploring for cancer immunotherapies is the “dendritic cell vaccine”. While there has been some success with these types of vaccines, they have encountered limitations as well. In a paper published today in Nature Methods, scientists describe a new approach to creating dendritic cell vaccines with higher precision and strength.
Traditional techniques for creating dendritic cell vaccines typically involve taking dendritic cells from the patient, “force-feeding” them with tumor antigens from a lab-grown tumor similar to the patient’s, then injecting the dendritic cells back into the patient. The use of a tumor that is similar, but not the same, has limited the vaccine’s effectiveness in the past as the antigens may differ from those of the patient’s tumor.
To capture antigens from the patient’s tumor, researchers at EPFL created artificial receptors called EVIRs (extracellular vesicle-internalizing receptors), which enable the dendritic cells to selectively and efficiently capture antigens. The EVIR inserted into the dendritic cell recognizes proteins on exosomes. Exosomes have become increasingly implicated in the promotion of metastasis and other cancer spreading mechanisms. Presenting antigens from exosomes can thus lead to higher activation of killer T cells.
Through imaging techniques, it was observed that these EVIRs also promote direct transfer of tumor antigens from the exosome surface to the outer membrane of the dendritic cell.
"This is a fascinating and unconventional route for antigen presentation to T cells, which does not require complex and rate-limiting molecular interactions inside the dendritic cell," explains Michelle de Palma who led the study.
The team plans to undergo future pre-clinical trials to further explore use of this technique’s effectiveness and safety in a clinical setting.
Image: Two images of EVIR-engineered dendritic cells (green) capturing tumor antigens in exosomes (gold/red). Cell nuclei are colored blue. Image courtesy of M. De Palma/EPFL.