Periodic Reporting for period 2 - EVOLVE (Extracellular Vesicle-Internalizing Receptors (EVIRs) for Cancer ImmunoGeneTherapy)
Reporting period: 2019-01-01 to 2020-06-30
In the reporting period we published several papers describing initial results of the project. In 2018 we have published a first paper describing the EVIR platform (Squadrito, Cianciaruso, Hansen & De Palma. Nature Methods, 2018). This work was initiated before the beginning of the project, but in the reporting period we undertook ERC-funded studies of the mechanism of antigen presentation by EVIR-engineered DCs (DC-EVIR), as planned in Aims 1 and 2 of the project. We obtained unexpected and exciting results indicating that the EVIR captures tumor-derived EVs and promotes cross-dressing of DCs with pre-formed tumor antigens in complex with MHCI. We also examined the effects of chemotherapy on tumor-derived EVs, which is relevant to applications of the DC-EVIR platform, as described in Aim 2 of the project, and published a paper reporting some of those findings (Keklikoglou*, Cianciaruso*, […] & De Palma. Nature Cell Biology, 2019). Moreover, we characterized by proteomics analysis various EV populations directly isolated from tumors; this is relevant to both exploring the antigenic repertoire of cancer-cell-derived EVs and identifying surface proteins that can be used to design new EVIRs (Aim 1). Some of the proteomics results have been published in 2019 (Cianciaruso*, Beltraminelli*, Duval*, […] & De Palma. Cell Reports, 2019). Finally, we published a Perspective article illustrating the state-of-the-art and prospects of engineering DC vaccines (Perez & De Palma. Nature Communications, 2019).
We are currently exploring the possibility to initiate a start-up company for the pre-clinical and clinical development of our bioengineering platform.