The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens and more particularly in which extracellular ligand binding is a scFV derived from an EGFRvIII monoclonal antibody conferring specific immunity against EGFRvIII positive cells. The TCR KO engineered immune cells endowed with such CARs are particularly suited for treating lung cancer anal cancers and glioblastoma multiforme.