This study describes the use of a previously reported chimerised
monoclonal antibody (mAb), ch2448, to kill human embryonic stem cells (hESCs) in vivo and prevent or delay the formation of
teratomas. ch2448 was raised against hESCs and was previously shown to effectively kill ovarian and
breast cancer cells in vitro and in vivo. The
antigen target was subsequently found to be
Annexin A2, an oncofetal
antigen expressed on both embryonic cells and
cancer cells. Against
cancer cells, ch2448 binds and kills via antibody-dependent cell-mediated cytotoxicity (ADCC) and/or
antibody-drug conjugate (ADC) routes. Here, we investigate if the use of ch2448 can be extended to hESC. ch2448 was found to bind specifically to undifferentiated hESC but not differentiated progenitors. Similar to previous study using
cancer cells, ch2448 kills hESC in vivo either indirectly by eliciting ADCC or directly as an ADC. The treatment with ch2448 post-
transplantation eliminated the in vivo circulating undifferentiated cells and prevented or delayed the formation of
teratomas. This surveillance role of ch2448 adds an additional layer of safeguard to enhance the safety and efficacious use of pluripotent stem cell-derived products in regenerative medicine. Thereby, translating the use of ch2448 in the treatment of
cancers to a proof of concept study in hESC (or pluripotent stem cell [PSC]), we show that mAbs can also be used to eliminate
teratoma forming cells in vivo during PSC-derived cell
therapies. We propose to use this strategy to
complement existing methods to eliminate
teratoma-forming cells in vitro. Residual undifferentiated cells may escape in vitro removal methods and be introduced into patients together with the differentiated cells.