CEA comprises highly repetitive immunoglobulin domains of A1-B1, A2-B2, and A3-B3. Some anti-CEA mAbs bind repetitive epitopes of CEA [51] and some are highly cross-reactive, lacking specificity to CEA [56] . The anti-CEA arm of MEDI-565 is a humanized version of the murine antibody A5B7, which has been shown to specifically bind to CEA [40, 56] . Characterizing the epitope of MEDI-565 has led us to propose that the critical residues F 326 , T 328 , and N 333 mediate the fine specificity to CEA of MEDI-565 due to their uniqueness in the A2 domain of CEA when compared with all other immunoglobulin domains of CEA and other related molecules of the CEACAM family, including CEACAM1, CEACAM3, CEACAM4, CEACAM6, CEACAM7, and CEACAM8.