Abstract: The invention pertains to bispecific antibodies having two antigen binding specificities, one binding to an epitope of NKG2-D type II integral membrane protein (NKG2D) and one binding to an antigen associated with a disease, preferably a tumor associated- or tumor specific antigen, such as ErbB2 (HER2), CD19, CD20, GD2, PD-L1, EGFR, or EGFRvIII. The bispecific molecules of the invention are preferably applied in the context of the treatment of tumor diseases or infectious diseases. Surprisingly it was found that the use of NKG2D binding specificities that bind in a competitive manner to the NKG2D receptor with its natural ligands such as MICA reduces or prevents the inhibitory effect of ligand shedding. Another advantage of the present invention lies in a synergistic combination of the bispecific molecules of the invention and chimeric antigen receptor (CAR) based therapy.