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Nicotinamide enhances natural killer cell function and yields remissions in patients with non-Hodgkin lymphoma.
Cichocki, Frank; Zhang, Bin; Wu, Cheng-Ying; Chiu, Emily; Day, Abderrahman; O'Connor, Roddy S; Yackoubov, Dima; Simantov, Ronit; McKenna, David H; Cao, Qing; Defor, Todd E; Janakiram, Murali; Wangen, Rose; Cayci, Zuzan; Snyder, Nathaniel; Kumar, Akhilesh; Grzywacz, Bartosz; Hwang, Justin; Geffen, Yona; Miller, Jeffrey S; Maakaron, Joseph; Bachanova, Veronika.
Affiliation
  • Cichocki F; Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
  • Zhang B; Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
  • Wu CY; Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
  • Chiu E; Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
  • Day A; Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
  • O'Connor RS; University of Minnesota Institute for Health Informatics, University of Minnesota, Minneapolis, MN 55455, USA.
  • Yackoubov D; Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Simantov R; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
  • McKenna DH; Gamida Cell, Jerusalem 91340, Israel.
  • Cao Q; Gamida Cell, Jerusalem 91340, Israel.
  • Defor TE; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
  • Janakiram M; Biostatistics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
  • Wangen R; Biostatistics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
  • Cayci Z; Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
  • Snyder N; Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
  • Kumar A; Division of Radiology, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
  • Grzywacz B; Metabolic Disease Research and Thrombosis Research Center, Departments of Cardiovascular Sciences, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19104, USA.
  • Hwang J; Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
  • Geffen Y; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
  • Miller JS; Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
  • Maakaron J; Gamida Cell, Jerusalem 91340, Israel.
  • Bachanova V; Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Sci Transl Med ; 15(705): eade3341, 2023 07 19.
Article de En | MEDLINE | ID: mdl-37467318
ABSTRACT
Allogeneic natural killer (NK) cell adoptive transfer has shown the potential to induce remissions in relapsed or refractory leukemias and lymphomas, but strategies to enhance NK cell survival and function are needed to improve clinical efficacy. Here, we demonstrated that NK cells cultured ex vivo with interleukin-15 (IL-15) and nicotinamide (NAM) exhibited stable induction of l-selectin (CD62L), a lymphocyte adhesion molecule important for lymph node homing. High frequencies of CD62L were associated with elevated transcription factor forkhead box O1 (FOXO1), and NAM promoted the stability of FOXO1 by preventing proteasomal degradation. NK cells cultured with NAM exhibited metabolic changes associated with elevated glucose flux and protection against oxidative stress. NK cells incubated with NAM also displayed enhanced cytotoxicity and inflammatory cytokine production and preferentially persisted in xenogeneic adoptive transfer experiments. We also conducted a first-in-human phase 1 clinical trial testing adoptive transfer of NK cells expanded ex vivo with IL-15 and NAM (GDA-201) combined with monoclonal antibodies in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) (NCT03019666). Cellular therapy with GDA-201 and rituximab was well tolerated and yielded an overall response rate of 74% in 19 patients with advanced NHL. Thirteen patients had a complete response, and 1 patient had a partial response. GDA-201 cells were detected for up to 14 days in blood, bone marrow, and tumor tissues and maintained a favorable metabolic profile. The safety and efficacy of GDA-201 in this study support further development as a cancer therapy.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Lymphome malin non hodgkinien / Interleukine-15 Limites: Humans Langue: En Journal: Sci Transl Med Sujet du journal: CIENCIA / MEDICINA Année: 2023 Type de document: Article Pays d'affiliation: États-Unis d'Amérique
Texte intégral
Ajouter à My VHL
Imprimer
XML
PubMed Links
Recherche sur Google

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Lymphome malin non hodgkinien / Interleukine-15 Limites: Humans Langue: En Journal: Sci Transl Med Sujet du journal: CIENCIA / MEDICINA Année: 2023 Type de document: Article Pays d'affiliation: États-Unis d'Amérique