The Role of Natural Killer Cells as a Platform for Immunotherapy in Pediatric Cancers

Abstract

Purpose of Review We aim to review the most recent findings in the use of NK cells in childhood cancers. Recent Findings Natural killer cells are cytotoxic to tumor cells. In pediatric leukemias, adoptive transfer of NK cells can bridge children not in remission to transplant. Interleukins (IL2, IL15) can enhance NK cell function. NK cell-CAR therapy has advantages of shorter life span that lessens chronic toxicities, lower risk of graft versus host disease when using allogeneic cells, ability of NK cells to recognize tumor cells that have downregulated MHC to escape T cells, and possibly less likelihood of cytokine storm. Cytotoxicity to solid tumors (rhabdomyosarcoma, Ewing’s sarcoma, neuroblastoma) is seen with graft versus tumor effect in transplant and in combination with antibodies. Challenges lie in the microenvironment which is suppressive for NK cells. Summary NK cell immunotherapy in childhood cancers is promising and recent works aim to overcome challenges.

NK cell predicts the severity of acute graft-versus-host disease in patients after allogeneic stem cell transplantation using antithymocyte globulin (ATG) in pretreatment scheme

“…The optimal balance between GVHD and GVL appears to be an excellent parameter to achieve long-term survival after allo-genetic stem cell transplantation. Previous study has showed that NK cells can eliminate leukemic cells, restore immunity early after stem cell transplant, while at the same time minimal graft versus host disease [15]. The use of a novel composite end point called GVHD-free progression-free survival (GPFS) was initiated in 2016 by Dr.Malard and colleagues.…”

Immunotherapies for pediatric cancer: current landscape and future perspectives

“…NK activation in the tumor microenvironment can also be an essential driver for dendritic cells and T cells to be recruited into the tumor site. Moreover, NK cells can be activated via ADCC through engaging CD16 (FcγRIIIA) with monoclonal antibodies such as daratumumab for targeting multiple myeloma and T-ALL or rituximab for treating B cell non-Hodgkin lymphoma [108,109].…”

Natural killer cells in patients with hematologic malignancies, solid tumors and in recipients of hematopoietic stem cell transplantation

“…Oncolytic virotherapy provokes the antitumor activity of NK cells by triggering antiviral immune responses [281]. NK cell immunotherapy has shown promising effects in the treatment of childhood solid tumors such as: rhabdomyosarcoma, Ewing's sarcoma, and neuroblastoma due to prominent GVT effects both in transplant setting and in combination with antibodies [282].…”