A TCR mimic monoclonal antibody for the HPV-16 E7-epitope p11-19/HLA-A*02:01 complex
by Tao Dao, Sungsoo Mun, Tatyana Korontsvit, Abdul G. Khan, Mary Ann Pohl, Thomas White, Martin G. Klatt, David Andrew, Ivo C. Lorenz, David A. Scheinberg
More effective treatments are needed for human papilloma virus (HPV)-induced cancers despite HPV virus vaccination. The oncogenic HPV protein targets are currently undruggable and intracellular and therefore there are no antibodies to these targets. Here we report the discovery of TCR mimic monoclonal antibodies (TCRm mAb) specific for the HPV E7 protein p11-19, YMLDLQPET, when presented on the cell surface in the context of HLA-A*02:01 by use of human phage display libraries. One of the mAbs, 3F8, was able to specifically mediate T cell- redirected cytotoxicity, in a bispecific T cell engager (BiTE) form. While further studies are required to assess the therapeutic potential of this approach, the study provided the proof of concept that TCRm mAb could be a therapeutic strategy for HPV-induced human cancers.