Raynier Devillier1,2, Boris Calmels3,4, Sophie Guia5, Mohammed Taha2, Cyril Fauriat2, Bechara Mfarrej3,4, Geoffroy Venton5, Eric Vivier5,6,7, Daniel Olive2, Christian Chabannon3,4, Didier Blaise1,2, Sophie Ugolini5. 1. Hematology Department, Institut Paoli-Calmettes, 13009 Marseille, France. 2. Immunity and Cancer Team, CRCM, Inserm Institut Paoli-Calmettes, Aix-Marseille Université, 13007 Marseille, France. 3. CRCM, Inserm Institut Paoli-Calmettes, Aix-Marseille Université, 13009 Marseille, France. 4. Module Biothérapies du Centre d'Investigations Cliniques de Marseille, Inserm Institut Paoli-Calmettes, Aix-Marseille Université, 13007 Marseille, France. 5. Centre d'Immunologie de Marseille-Luminy CIML, CNRS, INSERM, Aix Marseille Université, 13009 Marseille, France. 6. Assistance Publique des Hôpitaux de Marseille, Hôpital de la Timone, 13005 Marseille, France. 7. Innate Pharma, 13276 Marseille, France.
Abstract
Background: NK cell-based immunotherapy to prevent relapse after allogeneic transplantation is an appealing strategy because NK cells can provide strong antitumor effect without inducing graft-versus-host disease (GVHD). Thus, we designed a phase-I clinical trial evaluating the safety of a prophylactic donor-derived ex vivo IL-2 activated NK cell (IL-2 NK) infusion after allo-HSCT for patients with hematologic malignancies. Methods: Donor NK cells were purified and cultured ex vivo with IL-2 before infusion, at three dose levels. To identify the maximum tolerated dose was the main objective. In addition, we performed phenotypical and functional characterization of the NK cell therapy product, and longitudinal immune monitoring of NK cell phenotype in patients. Results: Compared to unstimulated NK cells, IL-2 NK cells expressed higher levels of activating receptors and exhibited increased degranulation and cytokine production in vitro. We treated 16 patients without observing any dose-limiting toxicity. At the last follow up, 11 out of 16 treated patients were alive in complete remission of hematologic malignancies without GVHD features and immunosuppressive treatment. Conclusions: Prophylactic donor-derived IL-2 NK cells after allo-HSCT is safe with low incidence of GVHD. Promising survivals and IL-2 NK cell activated phenotype may support a potential clinical efficacy of this strategy.
Background: NK cell-based immunotherapy to prevent relapse after allogeneic transplantation is an appealing strategy because NK cells can provide strong antitumor effect without inducing graft-versus-host disease (GVHD). Thus, we designed a phase-I clinical trial evaluating the safety of a prophylactic donor-derived ex vivo IL-2 activated NK cell (IL-2 NK) infusion after allo-HSCT for patients with hematologic malignancies. Methods: Donor NK cells were purified and cultured ex vivo with IL-2 before infusion, at three dose levels. To identify the maximum tolerated dose was the main objective. In addition, we performed phenotypical and functional characterization of the NK cell therapy product, and longitudinal immune monitoring of NK cell phenotype in patients. Results: Compared to unstimulated NK cells, IL-2 NK cells expressed higher levels of activating receptors and exhibited increased degranulation and cytokine production in vitro. We treated 16 patients without observing any dose-limiting toxicity. At the last follow up, 11 out of 16 treated patients were alive in complete remission of hematologic malignancies without GVHD features and immunosuppressive treatment. Conclusions: Prophylactic donor-derived IL-2 NK cells after allo-HSCT is safe with low incidence of GVHD. Promising survivals and IL-2 NK cell activated phenotype may support a potential clinical efficacy of this strategy.
Authors: Sophie Guia; Baptiste N Jaeger; Stefan Piatek; Sébastien Mailfert; Tomasz Trombik; Aurore Fenis; Nicolas Chevrier; Thierry Walzer; Yann M Kerdiles; Didier Marguet; Eric Vivier; Sophie Ugolini Journal: Sci Signal Date: 2011-04-05 Impact factor: 8.192
Authors: F Legrand; A-C Le Floch; A Granata; S Fürst; C Faucher; C Lemarie; S Harbi; S Bramanti; B Calmels; J El-Cheikh; C Chabannon; P-J Weiller; N Vey; L Castagna; D Blaise; R Devillier Journal: Bone Marrow Transplant Date: 2016-12-12 Impact factor: 5.483
Authors: Rizwan Romee; Maximillian Rosario; Melissa M Berrien-Elliott; Julia A Wagner; Brea A Jewell; Timothy Schappe; Jeffrey W Leong; Sara Abdel-Latif; Stephanie E Schneider; Sarah Willey; Carly C Neal; Liyang Yu; Stephen T Oh; Yi-Shan Lee; Arend Mulder; Frans Claas; Megan A Cooper; Todd A Fehniger Journal: Sci Transl Med Date: 2016-09-21 Impact factor: 17.956