Development of humanized rabbit monoclonal antibodies against vascular endothelial growth factor receptor 2 with potential antitumor effects

From rabbit antibody repertoires to rabbit monoclonal antibodies

“…In general, humanization strategies that have worked for mouse mAbs also work for rabbit mAbs, whether it is by rational design, 17, 33, 187 directed evolution 188 or a combination of both. 155, 189 As is the case for mouse mAbs, grafting of all six CDRs followed by iterative fine-tuning of framework residues is the most frequently used method for humanizing rabbit mAbs.…”

“…26, 27, 28, 29 Rabbit antibodies are able to recognize epitopes on human antigens that are not immunogenic in rodents, 30 increasing the total number of targetable epitopes and facilitating the generation of antibodies that cross-react with mouse orthologs of human antigens. 31, 32, 33 This is an important aspect for basic research and preclinical investigations with, for example, human tumor xenografts, where the presence or absence of on-target-off-tumor toxicities of therapeutic antibodies provides important information prior to clinical translation. In general, rabbit anti-mouse reactivity is valuable in mouse models of human disease and has also been exploited in basic research, for example, on mouse stem cell antigens.…”

The functional repertoire of rabbit antibodies and antibody discovery via next-generation sequencing

“…In the mid-1990s, development of a myeloma rabbit B-cell fusion partner 3 enabled the generation of stable rabbit hybridomas, also raising interest in rabbit V genes as substrate for development of therapeutic antibodies. Currently, humanized rabbit antibodies are undergoing validation as therapeutics, 4 with some having advanced to preclinical or early clinical development by emerging companies, e.g., Apexigen.…”

A novel rabbit anti-hepatocyte growth factor monoclonal neutralizing antibody inhibits tumor growth in prostate cancer cells and mouse xenografts

“…The lack of cross-reactivity with the mouse antigen is a major obstacle in the applications of monoclonal antibodies (mAbs) in the preclinical development, such as rilotumumab (AMG102), a monoclonal antibody against HGF, can be only tested in autocrine HGF/c-Metdependent human tumor xenograft models during preclinical stages [13,18], but not prostate cancer models. In the previous study, we have successfully a novel platform for efficiently generating rabbit monoclonal antibodies (RabMAbs) recognizing both human and mouse antigens and proved their better efficacy in vivo and in vitro than currently available drug in the market [19,20]. In this study, using the same technology, we generated and characterized a panel of anti-HGF RabMAbs neutralizing HGF/c-Met interaction.…”