Target molecules of existing anti-
cancer therapeutic
monoclonal antibodies (mAbs) are divided into 1) receptor-type
tyrosine kinases, such as human
epidermal growth factor receptor (HER) family, 2)
differentiation antigens, such as CD20 (
Rituxan target), 3) angiogenesis-related molecules, and 4)
immune checkpoint molecules (PD-1, etc.). We have recently reported a novel
therapy targeting lymphangiogenesis, but not angiogenesis, using an anti-LYVE-1 (lymphatic vessel endothelial
hyaluronan receptor 1) mAb. At present, many transporters are not considered to be target molecules for the
cancer therapy; however, our study strongly suggested that the inhibition of
cancer metabolism by mAbs against
amino acid transporters will play a significant role in future
cancer therapies. Most anti-
cancer therapeutic mAbs bind cell-surface molecules on viable
cancer cells: therefore, it is necessary to produce mAbs recognizing
epitopes on the extracellular domains of native and non-denatured
proteins. We concluded that viable
cancer cells or cells transfected with
cDNA encoding target
proteins are suitable immunogens for the production of anti-
cancer therapeutic mAbs. We introduce our efforts to develop seeds for therapeutic mAbs using whole
cancer cells and transfectants as the immunogen. As many target candidates in the future are multi-pass
membrane proteins, such as 12-pass
amino acid transporter proteins belonging to the solute carrier (SLC) family, and their possible immunogenic extracellular regions are small, the production of specific mAbs is highly difficult. In this review, we summarize the successful preparation and characterization of mAbs recognizing the extracellular domain of
oncoproteins, including transporters.