Abstract 14832: Immunologic Targeting of CD30 Eliminates Tumorigenic Human Pluripotent Stem Cells (iPSC) Allowing Safer Clinical Application of hiPSC-Based Therapy
Background: Human induced pluripotent stem cells (hiPSCs) are considered to be invaluable for regenerative medicine. However, they carry the risk of teratoma formation by residual undifferentiated cells, and it is important to develop a means of eliminating all residual tumorigenic cells before clinical application. Cell surface markers of hiPSCs can be useful for selective removal of undifferentiated hiPSCs from differentiated cultures. Although cell sorting strategies may be feasible, they are time-consuming and reduce cell viability. In this study, we hypothesized that cell selection using an antibody-cytotoxic drug conjugate may be clinically useful for immunologic targeting of undifferentiated cells.
Methods and Results: We first compared CD antigen expression patterns between undifferentiated and differentiated cells and found that CD30, CD50, TRA-1-60, and TRA-1-81 were highly expressed on undifferentiated cells. The CD30-negative fraction was less positive for Lin28, a pluripotent marker. To eliminate the CD30-positive fraction, we applied an anti-CD30 antibody-drug conjugate (brentuximab vedotin, Adcetris, SGN-35) that has been shown to be potent for selectively eliminating CD30-positive cells and has been already approved by the FDA for lymphoma therapy. Brentuximab vedotin treatment at 100 μg/ml for 72 hours blocked proliferation of hiPSCs, leading to cell death in vitro, but did not affect differentiated cells (fibroblasts and cardiomyocytes) (iPS and NHDF: 35-75% and 100% survival compared to untreated cells, respectively). Furthermore, hiPSC-derived cardiomyocytes treated with brentuximab vedotin showed reduced Lin28 expression compared to untreated hiPSC-derived cardiomyocytes (96 h, 100 μg/ml: 71.6%, 200 μg/ml: 26.6%; 120 h, 100 μg/ml: 46.7%, 200 μg/ml: 16.3%).
Conclusion: An anti-CD30 antibody-drug conjugate (brentuximab vedotin) eliminates residual undifferentiated hiPSCs from culture, which may enable safer clinical application of hiPSC-based cell therapy.
Author Disclosures: N. Sougawa: None. S. Masuda: None. S. Miyagawa: None. S. Fukushima: None. E. Ito: None. A. Saito: None. Y. Sawa: None.
- © 2014 by American Heart Association, Inc.