Immunotherapy has transformed healthcare and how physicians treat patients. Various forms of immunotherapy have been developed over the last two decades to target solid tumors and hematological malignancies. In the context of cancer, immune cells become altered and fail to recognize and target the rapidly proliferating mass of tumor cells. In response, immunotherapy redirects the existing immune population toward the tumor.
Although immunotherapy has improved clinical outcomes, efficacy remains limited. Tumors can evade the immune system and progress to other parts of the body. One specific cell type that can aid tumor progression includes dendritic cells. These specialized immune cells are known to activate T cells, a type of cell that targets cancer. Unfortunately, secreting factors by the tumor alter dendritic cell function, which prevents the activation of an immune response. Additionally, tumors express various markers, which allows them to evade detection. Tumor heterogeneity and the ability for tumors to shed makers allows cancer cells to adapt and become resistant to therapy. Scientists are working to improve current treatments and generate unique ways to enhance immune response.
A recent paper in Science Translational Medicine, by Dr. Michele De Palma and others, have developed a technique that improves dendritic cell function. Specifically, researchers have been able to engineer dendritic cells to target a broad range of cancer markers to minimize tumor evasion. De Palma is an Associate Professor in the School of Life Sciences at the Swiss Federal Technology Institute of Lausanne (EPFL). His work focuses on tumor resistance to therapy. Specifically, De Palma looks at immune cells that mediate resistance and aid in blood vessel formation that allow tumors to travel to other sites of the body. He is internationally known for his research in cancer biology and was awarded the Robert Wenner Prize for cancer research in 2017.
De Palma and his team used extracellular vesicles (EVs) to stimulate dendritic cell function. EVs are small vessels secreted by tumors that carry proteins and molecules, which the dendritic cell uses to activate the immune system. Since EVs come directly from the tumor, it would trigger a strong, more specific response. Previous work in De Palma’s lab used a receptor known as ‘EV-internalizing receptor’ (EVIR) to help mature dendritic cells and improve function. This new discovery builds off the concept of EVIR by enhancing its performance and generating proteins and other molecules that maintain dendritic cell function and survival. This new form of EVIR is referred to as instructive chimeric antigen receptor (iCAR), which further improves immune cell activation by dendritic cells.
This work programs dendritic cells in the body as opposed to in the lab and then reinfused in patients. The benefit to programming the cells inside the body is to provide more relevant tumor proteins necessary for dendritic cell function. The team hopes that by enhancing this process, they can provide more translational relevance for clinical use. De Palma and others have established a biotechnology company, EVIR Therapeutics, to produce this novel therapy for patients with cancer. Researchers are working toward bridging the gaps in research and clinical treatment to provide patients with novel and effective immunotherapies.
Paper, Science Translational Medicine, Michele De Palma, EPFL
