Manufacturing of Human T-lymphoid Progenitors from Two Different Hematopoietic Stem Cell Sources and Perspective for New Immunotherapies

Abstract

The adaptive immune system depends on the efficient response of lymphocytes, protecting the organism from infection or malignant diseases. T-cell immunodeficiency, innate or acquired, put the patient at risk for developing opportunistic infections and cancers. We previously described a novel approach to overcome the major limitations of T-cell immunotherapy and hematopoietic stem cell transplant (HSCT) by transplanting human T-lymphoid progenitors (HTLP), with the aim to achieve shortened immune reconstitution and fully functional naïve T-cell repertoire in immunodeficient or immunocompromised patients. By complementing our DL4-based cell culture with TNFα we developed and scaledup clinical strategies involving hematopoietic stem and progenitor cells (HSPC) differentiated into T-lymphoid progenitors. We discuss here recent advances made in the characterization of different cell sources used as starting materials for T-lymphoid progenitors manufacturing, as well as gene modification of these cells, highlighting new perspectives for the development of therapeutical strategies.