Novel super-high affinity sheep monoclonal antibodies against CEA bind colon and lung adenocarcinoma

We have developed technology to create monoclonal antibodies (MAbs) using l ymphocytes from immunized sheep. The affinities of these sheep monoclonal a ntibodies (SR IA) can be several orders of magnitude higher than mouse MAbs , This paper reports the development and validation of a modified enzyme-li nked immunoadsorbent assay (ELISA) method to select high-affinity antibodie s of the desired specificity at the first screen. Using this method, we hav e isolated high affinity SMA to carcinoembryonic antigen (CEA), a marker of colon cancer. Comparisons of our novel SMA with mouse MAbs using the new E LISA and BIAcore technology (BIAcore AB, Stevenage, Herts, UK) have confirm ed that we have made super-high affinity antibodies to CEA. One of these ha s a t(1/2) for dissociation of 8 days, which could provide a longer therape utic window than is available with murine monoclonals currently being used in the clinic. This antibody has a specific tissue staining profile; it thu s appears to be an excellent candidate for use in the clinic.