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Article

Treating iPSC-Derived β Cells with an Anti-CD30 Antibody–Drug Conjugate Eliminates the Risk of Teratoma Development upon Transplantation

by
Silvia Pellegrini
1,
Valentina Zamarian
1,
Elisa Landi
1,
Alessandro Cospito
1,
Marta Tiffany Lombardo
1,
Fabio Manenti
1,
Antonio Citro
1,
Marco Schiavo Lena
2,
Lorenzo Piemonti
1,3 and
Valeria Sordi
1,*
1
Diabetes Research Institute, IRCCS San Raffaele Hospital, Via Olgettina 60, 20132 Milan, Italy
2
Department of Pathology, IRCCS San Raffaele Hospital, 20132 Milan, Italy
3
Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(17), 9699; https://doi.org/10.3390/ijms23179699
Submission received: 1 August 2022 / Revised: 12 August 2022 / Accepted: 23 August 2022 / Published: 26 August 2022
(This article belongs to the Topic Stem Cell Differentiation and Applications)
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Abstract

Insulin-producing cells derived from induced pluripotent stem cells (iPSCs) are promising candidates for β cell replacement in type 1 diabetes. However, the risk of teratoma formation due to residual undifferentiated iPSCs contaminating the differentiated cells is still a critical concern for clinical application. Here, we hypothesized that pretreatment of iPSC-derived insulin-producing cells with an anti-CD30 antibody–drug conjugate could prevent in vivo teratoma formation by selectively killing residual undifferentiated cells. CD30 is expressed in all human iPSCs clones tested by flow cytometry (n = 7) but not in iPSC-derived β cells (iβs). Concordantly, anti-CD30 treatment in vitro for 24 h induced a dose-dependent cell death (up to 90%) in human iPSCs while it did not kill iβs nor had an impact on iβ identity and function, including capacity to secrete insulin in response to stimuli. In a model of teratoma assay associated with iβ transplantation, the pretreatment of cells with anti-CD30 for 24 h before the implantation into NOD-SCID mice completely eliminated teratoma development (0/10 vs. 8/8, p < 0.01). These findings suggest that short-term in vitro treatment with clinical-grade anti-CD30, targeting residual undifferentiated cells, eliminates the tumorigenicity of iPSC-derived β cells, potentially providing enhanced safety for iPSC-based β cell replacement therapy in clinical scenarios.
Keywords: induced pluripotent stem cells; beta cells; cell therapy; type 1 diabetes; teratoma; CD30 induced pluripotent stem cells; beta cells; cell therapy; type 1 diabetes; teratoma; CD30

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MDPI and ACS Style

Pellegrini, S.; Zamarian, V.; Landi, E.; Cospito, A.; Lombardo, M.T.; Manenti, F.; Citro, A.; Schiavo Lena, M.; Piemonti, L.; Sordi, V. Treating iPSC-Derived β Cells with an Anti-CD30 Antibody–Drug Conjugate Eliminates the Risk of Teratoma Development upon Transplantation. Int. J. Mol. Sci. 2022, 23, 9699. https://doi.org/10.3390/ijms23179699

AMA Style

Pellegrini S, Zamarian V, Landi E, Cospito A, Lombardo MT, Manenti F, Citro A, Schiavo Lena M, Piemonti L, Sordi V. Treating iPSC-Derived β Cells with an Anti-CD30 Antibody–Drug Conjugate Eliminates the Risk of Teratoma Development upon Transplantation. International Journal of Molecular Sciences. 2022; 23(17):9699. https://doi.org/10.3390/ijms23179699

Chicago/Turabian Style

Pellegrini, Silvia, Valentina Zamarian, Elisa Landi, Alessandro Cospito, Marta Tiffany Lombardo, Fabio Manenti, Antonio Citro, Marco Schiavo Lena, Lorenzo Piemonti, and Valeria Sordi. 2022. "Treating iPSC-Derived β Cells with an Anti-CD30 Antibody–Drug Conjugate Eliminates the Risk of Teratoma Development upon Transplantation" International Journal of Molecular Sciences 23, no. 17: 9699. https://doi.org/10.3390/ijms23179699

APA Style

Pellegrini, S., Zamarian, V., Landi, E., Cospito, A., Lombardo, M. T., Manenti, F., Citro, A., Schiavo Lena, M., Piemonti, L., & Sordi, V. (2022). Treating iPSC-Derived β Cells with an Anti-CD30 Antibody–Drug Conjugate Eliminates the Risk of Teratoma Development upon Transplantation. International Journal of Molecular Sciences, 23(17), 9699. https://doi.org/10.3390/ijms23179699

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