NK-Cell Therapy in the Setting of Haploidentical Hematopoietic Stem Cell Transplantation

The use of cellular immunotherapy has increased significantly overthe past decade. Growing understanding of NK cell biology and theirpotent anti-cancer and infectious activity sustained the development ofNK cell therapy for patients with hematologic disorders. In the settingof haploidentical hematopoietic stem cell transplantation (HSCT),while NK cells are the first subset to recover, we and others reportedthat NK cells generated after selected CD34+ HSCT exhibit an immaturephenotype in association with impaired functions. In the same way, afterhaploidentical HSCT with posttransplant cyclophosphamide (PT-Cy), themajority of mature NK cells infused with unmanipulated grafts are lostupon PT-Cy administration. Thus, blunting of Nk cell alloréactivity inthis transplantation setting support the adoptive transfer of alloreactivehaploidentical donor NK cells. A major challenge to the broaderapplication of adoptive NK cell therapy is to improve methods for in vitroexpansion of low-frequency NK cells. Large-scale expansions have beenobtained with various feeder cell-based systems but these methods havemajor drawbacks including complicated procedures, safety issues and/or the expansion of exhausted NK cells. Developing innovative strategies togenerate clinically efficient NK cells with minimal in vitro manipulation,in large numbers, would provide an important breakthrough in NK cellbasedimmunotherapy. We will discuss major clinical trial providing asolid basis for the development of NK cell therapies and report our ownexperience.

کلیدواژه ها:

Immunotherapy ، Haploidentical hematopoietic stem cell transplantation ، NK cells