Janneke S Hoogstad-van Evert1, Ruud Bekkers2, Nelleke Ottevanger3, Joop H Jansen4, Leon Massuger5, Harry Dolstra4. 1. Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Obstetrics and Gynecology, Amphia Hospital, Breda, the Netherlands. Electronic address: Janneke.Hoogstad-vanEvert@Radboudumc.nl. 2. Department of Obstetrics and Gynecology, Catharina Ziekenhuis, Eindhoven, the Netherlands; GROW school for oncology and developmental biology, Maastricht University Medical Centre, the Netherlands. 3. Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands. 4. Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands. 5. Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, the Netherlands.
Abstract
INTRODUCTION: Adoptive cellular immunotherapy could be an interesting new treatment option for ovarian carcinoma (OC), as research has demonstrated that OC is an immunogenic disease. In particular, natural killer (NK) cells have attracted attention due to their ability to kill tumor cells without prior sensitization. The therapeutic value of allogeneic NK cells has been first observed in hematological cancers and is increasingly being explored in solid tumors. METHODS: To substantiate the rationale for NK cell therapy in OC we performed a literature search in the Pubmed database and in the international trial register clinicaltrials.gov with attention for the effect of OC on NK cell function, the effect of current treatment on NK cell biology and the evidence on the therapeutic value of NK cell therapy against OC. RESULTS: In six clinical trials only 31 OC patients have been reported that received NK cell adoptive transfer. The majority of patients reached stable disease after NK cell therapy, with a mild pattern of side effects. In patients who received repeated infusions, more complete responses are described. All reported studies investigated the intravenous infusion of NK cells. Whereas the studies that are currently recruiting, investigate intraperitoneal infusion of allogeneic NK cells. CONCLUSION: In this review the pre-clinical evidence and current trials on NK cell immunotherapy in OC patients are summarized. Furthermore, challenges that have to be overcome for NK cell adoptive therapy to have a significant impact on disease outcome are discussed.
INTRODUCTION: Adoptive cellular immunotherapy could be an interesting new treatment option for ovarian carcinoma (OC), as research has demonstrated that OC is an immunogenic disease. In particular, natural killer (NK) cells have attracted attention due to their ability to kill tumor cells without prior sensitization. The therapeutic value of allogeneic NK cells has been first observed in hematological cancers and is increasingly being explored in solid tumors. METHODS: To substantiate the rationale for NK cell therapy in OC we performed a literature search in the Pubmed database and in the international trial register clinicaltrials.gov with attention for the effect of OC on NK cell function, the effect of current treatment on NK cell biology and the evidence on the therapeutic value of NK cell therapy against OC. RESULTS: In six clinical trials only 31 OCpatients have been reported that received NK cell adoptive transfer. The majority of patients reached stable disease after NK cell therapy, with a mild pattern of side effects. In patients who received repeated infusions, more complete responses are described. All reported studies investigated the intravenous infusion of NK cells. Whereas the studies that are currently recruiting, investigate intraperitoneal infusion of allogeneic NK cells. CONCLUSION: In this review the pre-clinical evidence and current trials on NK cell immunotherapy in OCpatients are summarized. Furthermore, challenges that have to be overcome for NK cell adoptive therapy to have a significant impact on disease outcome are discussed.
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