title: Poly(phosphorhydrazone) dendrimers: yin and yang of monocyte activation for human NK cell amplification applied to immunotherapy against multiple myeloma.
abstract: Human natural killer (NK) cells play a key role in anti-cancer and anti-viral immunity, but their selective amplification in vitro is extremely tedious to achieve and remains one of the most challenging problems to solve for efficient NK cell-based immuno-therapeutic treatments against malignant diseases. Here we report that, when added to ex vivo culture of peripheral blood mononuclear cells from healthy volunteers or from cancer patients with multiple myeloma, poly (phosphorhydrazone) dendrimers capped with amino-bis(methylene phosphonate) end groups enable the efficient proliferation of NK cells with anti-cancer cytotoxicity in vivo. We also show that the amplification of the NK population relies on the preliminary activation of monocytes in the framework of a multistep cross-talk between monocytes and NK cells before the proliferation thereof. Thus poly(phosphorhydrazone) dendrimers represent a novel class of extremely promising drugs to develop NK-cell based anti-cancer therapies.
authors: Centre de Recherche en Cancérologie de Toulouse, Université de Toulouse, CNRS, INSERM, UPS, France.
authors: Mary
authors: M
authors: Poupot
authors: LCC-CNRS, Université de Toulouse, CNRS, France.
authors: Cédric-Olivier
authors: CO
authors: Turrin
authors: LCC-CNRS, Université de Toulouse, CNRS, France.
authors: Anne-Marie
authors: AM
authors: Caminade
authors: Centre de Recherche en Cancérologie de Toulouse, Université de Toulouse, CNRS, INSERM, UPS, France.
authors: Jean-Jacques
authors: JJ
authors: Fournié
authors: Institut Universitaire du Cancer de Toulouse-Oncopôle, Université de Toulouse, CNRS, INSERM, UPS, France.
authors: Michel
authors: M
authors: Attal
authors: Centre de Physiopathologie de Toulouse-Purpan, Université de Toulouse, CNRS, INSERM, UPS, France.
authors: Rémy
authors: R
authors: Poupot
authors: Centre de Physiopathologie de Toulouse-Purpan, Université de Toulouse, CNRS, INSERM, UPS, France. Electronic address: severine.fruchon@inserm.fr.
authors: Séverine
authors: S
authors: Fruchon
mesh_terms: D050091:Dendrimers / Q000494:pharmacology*; D006801:Humans; D007167:Immunotherapy; D007694:Killer Cells, Natural; D007963:Leukocytes, Mononuclear; D009000:Monocytes; D009101:Multiple Myeloma / Q000628:therapy*
chemical_list: D050091:Dendrimers
keywords: Cancer immunotherapy; Dendrimers; Monocytes; Multiple myeloma; NK cells