Opportunities for Antibody Discovery Using Human Pluripotent Stem Cells: Conservation of Oncofetal Targets.

Heng Liang Tan,Andre Choo

doi:10.3390/ijms20225752

Abstract

Pluripotent stem cells (PSCs) comprise both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). The application of pluripotent stem cells is divided into four main areas, namely: (i) regenerative therapy, (ii) the study and understanding of developmental biology, (iii) drug screening and toxicology and (iv) disease modeling. In this review, we describe a new opportunity for PSCs, the discovery of new biomarkers and generating antibodies against these biomarkers. PSCs are good sources of immunogen for raising monoclonal antibodies (mAbs) because of the conservation of oncofetal antigens between PSCs and cancer cells. Hence mAbs generated using PSCs can potentially be applied in two different fields. First, these mAbs can be used in regenerative cell therapy to characterize the PSCs. In addition, the mAbs can be used to separate or eliminate contaminating or residual undifferentiated PSCs from the differentiated cell product. This step is critical as undifferentiated PSCs can form teratomas in vivo. The mAbs generated against PSCs can also be used in the field of oncology. Here, novel targets can be identified and the mAbs developed as targeted therapy to kill the cancer cells. Conversely, as new and novel oncofetal biomarkers are discovered on PSCs, cancer mAbs that are already approved by the FDA can be repurposed for regenerative medicine, thus expediting the route to the clinics.

Highlights

Pluripotent stem cells (PSCs) comprise both embryonic stem cells (ESCs) and induced pluripotent stem cells [1,2]
In addition to characterizing PSCs, we demonstrated the utilities of our monoclonal antibodies (mAbs) in both regenerative cell therapy and oncology
These mAbs were found to bind cancer cells due to the conservation of oncofetal targets between embryonic and cancer cells. These studies provided the opportunities for the identification of novel conserved antigens, and interestingly, the majority of the antigen targets, which are expressed on both PSCs and cancer cells, are glycoproteins

Summary

Introduction

Pluripotent stem cells (PSCs) comprise both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) [1,2]. Some of the mAbs bind to cancer cells as a result of oncofetal antigen conservation and have been developed as targeted therapies to treat cancers [34,35] Besides their use to characterize PSCs, mAbs can be used to separate undifferentiated cells from the differentiated cell product, especially if the antigen is downregulated in the latter. Tang et al reported of a mAb, SSEA-5, which binds to the glycan H type 1 that is highly and expressed in PSCs [49] In their study, they showed that a combination of SSEA-5 with two other pluripotent surface markers is sufficient to remove teratoma formation potential of PSCs. Recently, our group proposed a strategy to complement existing methods that eliminate teratoma-forming cells in vitro [50]. In addition to using them to characterize PSCs, these mAbs can be used in combination to separate and ”clean up” the undifferentiated PSCs from final cell products, prevent teratoma formation in vivo and make PSC-derived regenerative cell therapies safer

H Type 1

Findings

Discussion