Induced pluripotent stem cells: challenges and opportunities for cancer immunotherapy
- Sir William Dunn School of Pathology, University of Oxford, Oxford, UK
Despite recent advances in cancer treatment over the past 30 years, therapeutic options remain limited and do not always offer a cure for malignancy. Given that tumor-associated antigens (TAA) are, by definition, self-proteins, the need to productively engage autoreactive T cells remains at the heart of strategies for cancer immunotherapy. These have traditionally focused on the administration of autologous monocyte-derived dendritic cells (moDC) pulsed with TAA, or the ex vivo expansion and adoptive transfer of tumor-infiltrating lymphocytes (TIL) as a source of TAA-specific cytotoxic T cells (CTL). Although such approaches have shown some efficacy, success has been limited by the poor capacity of moDC to cross present exogenous TAA to the CD8+ T-cell repertoire and the potential for exhaustion of CTL expanded ex vivo. Recent advances in induced pluripotency offer opportunities to generate patient-specific stem cell lines with the potential to differentiate in vitro into cell types whose properties may help address these issues. Here, we review recent success in the differentiation of NK cells from human induced pluripotent stem (iPS) cells as well as minor subsets of dendritic cells (DCs) with therapeutic potential, including CD141+XCR1+ DC, capable of cross presenting TAA to naïve CD8+ T cells. Furthermore, we review recent progress in the use of TIL as the starting material for the derivation of iPSC lines, thereby capturing their antigen specificity in a self-renewing stem cell line, from which potentially unlimited numbers of naïve TAA-specific T cells may be differentiated, free of the risks of exhaustion.
Keywords: cancer, immunotherapy, dendritic cell, cytotoxic T cell, NK cell, pluripotency, iPS cell
Citation: Sachamitr P, Hackett S and Fairchild PJ (2014) Induced pluripotent stem cells: challenges and opportunities for cancer immunotherapy. Front. Immunol. 5:176. doi: 10.3389/fimmu.2014.00176
Received: 10 February 2014; Accepted: 03 April 2014;
Published online: 17 April 2014.
Edited by:Fang-Ping Huang, Imperial College London, UK
Reviewed by:Angel Porgador, Ben-Gurion University of the Negev, Israel
Kerry Campbell, Fox Chase Cancer Center, USA
Copyright: © 2014 Sachamitr, Hackett and Fairchild. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Paul Jonathan Fairchild, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK e-mail: firstname.lastname@example.org
†Patty Sachamitr and Simon Hackett have contributed equally to this work.