TY - JOUR TI - A DL-4- and TNFα-based culture system to generate high numbers of nonmodified or genetically modified immunotherapeutic human T-lymphoid progenitors AU - Moirangthem, Ranjita Devi AU - Ma, Kuiying AU - Lizot, Sabrina AU - Cordesse, Anne AU - Olivré, Juliette AU - de Chappedelaine, Corinne AU - Joshi, Akshay AU - Cieslak, Agata AU - Tchen, John AU - Cagnard, Nicolas AU - Asnafi, Vahid AU - Rausell, Antonio AU - Simons, Laura AU - Zuber, Julien AU - Taghon, Tom AU - Staal, Frank J. T. AU - Pflumio, Françoise AU - Six, Emmanuelle AU - Cavazzana, Marina AU - Lagresle-Peyrou, Chantal AU - Soheili, Tayebeh AU - André, Isabelle T2 - Cellular & Molecular Immunology AB - Several obstacles to the production, expansion and genetic modification of immunotherapeutic T cells in vitro have restricted the widespread use of T-cell immunotherapy. In the context of HSCT, delayed naïve T-cell recovery contributes to poor outcomes. A novel approach to overcome the major limitations of both T-cell immunotherapy and HSCT would be to transplant human T-lymphoid progenitors (HTLPs), allowing reconstitution of a fully functional naïve T-cell pool in the patient thymus. However, it is challenging to produce HTLPs in the high numbers required to meet clinical needs. Here, we found that adding tumor necrosis factor alpha (TNFα) to a DL-4-based culture system led to the generation of a large number of nonmodified or genetically modified HTLPs possessing highly efficient in vitro and in vivo T-cell potential from either CB HSPCs or mPB HSPCs through accelerated T-cell differentiation and enhanced HTLP cell cycling and survival. This study provides a clinically suitable cell culture platform to generate high numbers of clinically potent nonmodified or genetically modified HTLPs for accelerating immune recovery after HSCT and for T-cell-based immunotherapy (including CAR T-cell therapy). DA - 2021/06/11/ PY - 2021 DO - 10.1038/s41423-021-00706-8 DP - www.nature.com SP - 1 EP - 15 J2 - Cell Mol Immunol LA - en SN - 2042-0226 UR - https://www.nature.com/articles/s41423-021-00706-8 Y2 - 2021/06/11/22:19:48 ER -