Résumé
It has been previously demonstrated that tumor cells expressing MICA are no more able to grow in vivo due to the killing of tumor cells by both NK and CD8+ T cells.
In order to restore the presence of the MICA ligand at the surface of tumor cells, we designed biomolecules composed of MICA and an scFv (single chain fragment variable) that can recognise tumor associated antigens (TAA). The biomolecules should target tumor cells and re-direct the specific lysis of tumor cells by NK cells after interaction between NKG2D and exogenous MICA at the surface of tumor cells.
In vitro cytometry experiments showed that the biomolecules specifically bind different tumor cells expressing TAA. Using 51Cr release assay, we demonstrated that the biomolecules induce an efficient and specific killing of tumor cells mediated by NK cells or human PMBCs. In vivo, biodistribution studies showed that the biomolecules could target xenografted tumor when injected intravenously. Consequently, a protocol is investigated for therapy.