Ex vivo-expanded and activated haploidentical natural killer cells infusion before autologous stem cell transplantation in high-risk neuroblastoma: a phase I/II pilot study.

Mohammad Ahmadvand, Ghasem Janbabai, Bahram Chahardouli, Amir Kasaeian, Tahereh Rostami, Morteza Azari, Mohammad Reza Shemshadi Nia, Mojtaba Azari, Mohammad Reza Rostami, Ramin Ahangar-Sirous, Azadeh Kiumarsi

Journal: Cancer immunology, immunotherapy : CII 2025;74(5):160

PMID: 40131534

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Abstract

Given that natural killer (NK; CD3 - CD56 +) cells-mediated antibody-dependent cell cytotoxicity (ADCC) plays an important role in targeting neuroblastoma (NB) cells, adoptive cell therapy (ACT) utilizing expanded and activated haploidentical NK cells has emerged as a promising immunotherapeutic approach in pediatric patients with high-risk NB. In this pilot study, five pediatric patients with high-risk NB were enrolled. After harvesting hematopoietic progenitor cells (HPCs), patients received an intravenous infusion of high-activity iodine-131 (I)-meta-iodobenzylguanidine (I-MIBG). Seven days after the I-MIBG infusion and before the delivery of a single infusion of haploidentical purified NK cells, patients were administered a preparative regimen to establish a lymphodepleted host environment conducive to improved donor NK cell survival. Four days after the NK cell infusion, patients underwent the conditioning regimen, then received autologous hematopoietic stem cell transplantation (AHSCT). All patients achieved successful neutrophil and platelet engraftment. No adverse reactions were noted during or after the infusion of NK cells. Our study shows that incorporating NK cell infusion before AHSCT as a component of the conditioning regimen for consolidative therapy in pediatric patients with high-risk NB can be safe and well tolerated. IRCT Registration Number: IRCT20140818018842N32.

Address: Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. [email protected].; Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. [email protected].; Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.; Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.; Research Center for Chronic Inflammatory Diseases, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.; Clinical Research Development Unit, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.; Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.; Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.; Department of Pediatrics, School of Medicine, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. [email protected].

DOI: 10.1007/s00262-025-03990-9