title: Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo.
abstract: As significant numbers of acute myeloid leukemia (AML) patients are still refractory to conventional therapies or experience relapse, immunotherapy using T cells expressing chimeric antigen receptors (CARs) might represent a valid treatment option. AML cells frequently overexpress the myeloid antigens CD33 and CD123, for which specific CARs can be generated. However, CD33 is also expressed on normal hematopoietic stem/progenitor cells (HSPCs), and its targeting could potentially impair normal hematopoiesis. In contrast, CD123 is widely expressed by AML, while low expression is detected on HSPCs, making it a much more attractive target. In this study we describe the in vivo efficacy and safety of using cytokine-induced killer (CIK) cells genetically modified to express anti-CD33 or anti-CD123 CAR to target AML. We show that both these modified T cells are very efficient in reducing leukemia burden in vivo, but only the anti-CD123 CAR has limited killing on normal HSPCs, thus making it a very attractive immunotherapeutic tool for AML treatment.
authors: 1] Department of Pediatrics, Centro di Ricerca 'Matilde Tettamanti', University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy [2] Haematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London, UK.
authors: I
authors: I
authors: Pizzitola
authors: Haematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London, UK.
authors: F
authors: F
authors: Anjos-Afonso
authors: Haematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London, UK.
authors: K
authors: K
authors: Rouault-Pierre
authors: Haematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London, UK.
authors: F
authors: F
authors: Lassailly
authors: Department of Pediatrics, Centro di Ricerca 'Matilde Tettamanti', University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy.
authors: S
authors: S
authors: Tettamanti
authors: Department of Haematology, Ospedale Riuniti, Bergamo, Italy.
authors: O
authors: O
authors: Spinelli
authors: Department of Pediatrics, Centro di Ricerca 'Matilde Tettamanti', University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy.
authors: A
authors: A
authors: Biondi
authors: Department of Pediatrics, Centro di Ricerca 'Matilde Tettamanti', University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy.
authors: E
authors: E
authors: Biagi
authors: Haematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London, UK.
authors: D
authors: D
authors: Bonnet
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D055612:Cytokine-Induced Killer Cells / Q000276:immunology*; D006801:Humans; D053650:Interleukin-3 Receptor alpha Subunit / Q000037:antagonists & inhibitors*; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D011946:Receptors, Antigen / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C571163:CD33 protein, human; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; D011946:Receptors, Antigen; D011993:Recombinant Fusion Proteins; D063268:Sialic Acid Binding Ig-like Lectin 3