Monoclonal antibodies are being produced by new technologies such as phage display libraries or using a """"""""humanized"""""""" mouse. The advantage of such technologies is that totally human mAbs are produced and are predicted to be less immunogenic in humans than rodent, non-human primate, chimeric or humanized mAbs. Monoclonal antibodies that are non-immunogenic will be more successful therapeutic agents than immunogenic mAbs. A potential disadvantage of mAbs generated by phage display libraries is that the VH-VL pairs selected by screening antigen in vitro may not be the same as those pairs selected during the course of a normal immune response. In vivo, VH-VL pairs undergo both positive and negative selection. In vitro screening could create VH-VL pairs that are also autospecific, could select underutilzed V genes or could create unusuall pairs that might be immunogenic. To study the question of whether or not monoclonal antibodies produced by novel technologies create """"""""normal"""""""", """"""""autospecific"""""""" or """"""""unusual"""""""" VH-VL pairs, we have generated a hybridoma library from a BALB/c mouse immunized with tetanus toxoid. A phage display library from the same mouse is under construction. Analysis of the hybridomas shows a diverse response in this mouse with a least 8 different anti-tetanus toxoid clones utilizing four different VH families and 8 different VL families. The repertoire of the phage display library will be compared to that of the hybridoma library
