Use of Allogeneic NK Cells for Cancer Immunotherapy

Abstract

Controversy exists as to the role that the immune system plays in cancer therapy. While the immune system has been proposed to scavenge the body to prevent microscopic transformation from forming cancer, it has been difficult to mount its potential of shrinking established tumors. NK cells are components of the innate immune system. They can recognize targets without prior sensitization, making them ideal candidates to manipulate for therapeutic use against cancer. Initially, autologous NK cells were directed against tumors but it was realized that NK cells that recognize self cells are inhibited. More encouraging advances have been made with allogeneic NK cell therapy in clinical trials to overcome this limitation. In this article, we present developments in NK cell adoptive immunotherapy for hematologic and solid tumor malignancies.

Heterodimeric Bispecific Single-Chain Variable-Fragment Antibodies Against EpCAM and CD16 Induce Effective Antibody-Dependent Cellular Cytotoxicity Against Human Carcinoma Cells

“…Although engaging T-cells show promise, past successes have taught us that the populations of NK cells also can readily be expanded in patients, and NK cells can be powerful killers of tumor cells. 31 By themselves, NK cells are marginally effective against carcinomas. However, using the bispecific scFV platform that we call BiKEs, NK cells can be effectively recruited to kill even those carcinomas that have shed class 1 histocompatibility markers to avoid T-cell killing.…”

Acute GVHD in patients receiving IL-15/4-1BBL activated NK cells following T-cell–depleted stem cell transplantation

“…[1][2][3] The potential for NK cells to mediate antitumor effects has been of particular interest in allogeneic hematopoietic stem cell transplantation (HSCT) (reviewed in Foley et al, 4 Leung, 5 and Locatelli et al 6 ), fueled by animal studies demonstrating that NK cells can facilitate engraftment and augment graft-versus-tumor effects without mediating graft-versus-host disease (GVHD). [7][8][9] Current models hold that this results from differential expression of ligands for NKactivating receptors on malignant cells and hematopoietic cells vs healthy nonhematopoietic tissues.…”

Combined IL-15 and IL-12 drives the generation of CD34+-derived natural killer cells with superior maturation and alloreactivity potential following adoptive transfer

“…1 In the context of allogeneic hematopoietic stem cell transplantation (HSCT), it is well established that fast repopulating alloreactive NK cells mediate an efficient graft-versus-leukemia reaction and improve control of relapse without causing graft-versus-host disease. [2][3][4] Importantly, prolonged relapse-free survival has been demonstrated in allotransplanted AML patients in the setting of killer immunoglobulin-like receptor (KIR)-ligand mismatch between patients and allogeneic donors.…”