The present invention provides, inter alia, isolated monoclonal and polyclonal anti-tumor endothelial marker 8 (TEM8) antibodies or antigen binding fragments thereof that (a) bind to TEM8 membrane antigen in its native form occurring on the surface of a tumor cell (b) may be internalized by a tumor cell (c) bind strongly to tumor cells but not or only minimally to cells which lack expression of TEM8 and (d) are characterized in that the mean fluorescence intensity (MFI) of the antibody or an antigen binding fragment thereof against a mammalian cell line expressing TEM8 is at least two times higher than the MFI against the mammalian cell line not expressing TEM8 at antigen saturation. Chimeric antigen receptors (CARs) including an antigen binding fragment of such antibodies, modified antibodies, compositions, pharmaceutical compositions, and kits including the antibodies according to the present invention, and methods of use are also provided.
