Classification of current anticancer immunotherapies

// Lorenzo Galluzzi 1,2,3,4,* , Erika Vacchelli 1,2,3 , José-Manuel Bravo-San Pedro 1,2,3 , Aitziber Buqué 1,2,3 , Laura Senovilla 1,2,3 , Elisa Elena Baracco 1,2,3,5 , Norma Bloy 1,2,3,5 , Francesca Castoldi 1,2,3,5,6 , Jean-Pierre Abastado 7 , Patrizia Agostinis 8 , Ron N. Apte 9 , Fernando Aranda 1,2,3,10 , Maha Ayyoub 11,12 , Philipp Beckhove 13 , Jean-Yves Blay 14,15 , Laura Bracci 16 , Anne Caignard 17,18 , Chiara Castelli 19 , Federica Cavallo 20 , Estaban Celis 21 , Vincenzo Cerundolo 22 , Aled Clayton 23,24 , Mario P. Colombo 19 , Lisa Coussens 25 , Madhav V. Dhodapkar 26 , Alexander M. Eggermont 3 , Douglas T. Fearon 27 , Wolf H. Fridman 2,4,28,29 , Jitka Fučíková 6,30 , Dmitry I. Gabrilovich 31 , Jérôme Galon 2,4,28,32 , Abhishek Garg 8 , François Ghiringhelli 33,34,35 , Giuseppe Giaccone 36,37 , Eli Gilboa 38 , Sacha Gnjatic 39 , Axel Hoos 40 , Anne Hosmalin 4,41,42,43 , Dirk Jäger 44 , Pawel Kalinski 45,46,47 , Klas Kärre 48 , Oliver Kepp 1,2,49 , Rolf Kiessling 50 , John M. Kirkwood 51 , Eva Klein 48 , Alexander Knuth 52 , Claire E. Lewis 53 , Roland Liblau 54,55,56 , Michael T. Lotze 45,46 , Enrico Lugli 57 , Jean-Pierre Mach 58 , Fabrizio Mattei 16 , Domenico Mavilio 57,59 , Ignacio Melero 60,61 , Cornelis J. Melief 62,63 , Elizabeth A. Mittendorf 64 , Lorenzo Moretta 65 , Adekunke Odunsi 66 , Hideho Okada 67 , Anna Karolina Palucka 68 , Marcus E. Peter 69 , Kenneth J. Pienta 70 , Angel Porgador 9 , George C. Prendergast 71,72,73 , Gabriel A. Rabinovich 74 , Nicholas P. Restifo 75 , Naiyer Rizvi 76 , Catherine Sautès-Fridman 2,4,28,29 , Hans Schreiber 77 , Barbara Seliger 78 , Hiroshi Shiku 79 , Bruno Silva-Santos 80 , Mark J. Smyth 81,82 , Daniel E. Speiser 83,84 , Radek Spisek 6,30 , Pramod K. Srivastava 85,86 , James E. Talmadge 87 , Eric Tartour 4,88,89,90 , Sjoerd H. Van Der Burg 91 , Benoît J. Van Den Eynde 92,93,94 , Richard Vile 95 , Hermann Wagner 96 , Jeffrey S. Weber 97 , Theresa L. Whiteside 46,98 , Jedd D. Wolchok 99,100 , Laurence Zitvogel 3,101,102 , Weiping Zou 103 and Guido Kroemer 1,2,4,49,104,* 1 Equipe 11 labellisée pas la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France 2 INSERM, U1138, Paris, France 3 Gustave Roussy Cancer Campus, Villejuif, France 4 Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France 5 Faculté de Medicine, Université Paris Sud/Paris XI, Le Kremlin-Bicêtre, France 6 Sotio a.c., Prague, Czech Republic 7 Pole d’innovation thérapeutique en oncologie, Institut de Recherches Internationales Servier, Suresnes, France 8 Cell Death Research and Therapy (CDRT) Laboratory, Dept. of Cellular and Molecular Medicine, University of Leuven, Leuven, Belgium 9 The Shraga Segal Dept. of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel 10 Group of Immune receptors of the Innate and Adaptive System, Institut d’Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain 11 INSERM, U1102, Saint Herblain, France 12 Institut de Cancérologie de l’Ouest, Saint Herblain, France 13 Translational Immunology Division, German Cancer Research Center, Heidelberg, Germany 14 Equipe 11, Centre Léon Bérard (CLR), Lyon, France 15 Centre de Recherche en Cancérologie de Lyon (CRCL), Lyon, France 16 Dept. of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy 17 INSERM, U1160, Paris, France 18 Groupe Hospitalier Saint Louis-Lariboisière – F. Vidal, Paris, France 19 Unit of Immunotherapy of Human Tumors, Dept. of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy 20 Molecular Biotechnology Center, Dept. of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy 21 Cancer Immunology, Inflammation and Tolerance Program, Georgia Regents University Cancer Center, Augusta, GA, USA 22 MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK 23 Institute of Cancer & Genetics, School of Medicine, Cardiff University, Cardiff, UK 24 Velindre Cancer Centre, Cardiff, UK 25 Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA 26 Sect. of Hematology and Immunobiology, Yale Cancer Center, Yale University, New Haven, CT, USA 27 Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA 28 Université Pierre et Marie Curie/Paris VI, Paris, France 29 Equipe 13, Centre de Recherche des Cordeliers, Paris, France 30 Dept. of Immunology, 2nd Faculty of Medicine and University Hospital Motol, Charles University, Prague, Czech Republic 31 Dept. of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA 32 Laboratory of Integrative Cancer Immunology, Centre de Recherche des Cordeliers, Paris, France 33 INSERM, UMR866, Dijon, France 34 Centre Georges François Leclerc, Dijon, France 35 Université de Bourgogne, Dijon, France 36 Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA 37 Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA 38 Dept. of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL, USA 39 Sect. of Hematology/Oncology, Immunology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA 40 Glaxo Smith Kline, Cancer Immunotherapy Consortium, Collegeville, PA, USA 41 INSERM, U1016, Paris, France 42 CNRS, UMR8104, Paris, France 43 Hôpital Cochin, AP-HP, Paris, France 44 National Center for Tumor Diseases, University Medical Center Heidelberg, Heidelberg, Germany 45 Dept. of Surgery, University of Pittsburgh, Pittsburgh, PA, USA 46 University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA, USA 47 Dept. of Immunology and Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA 48 Dept. of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden 49 Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France 50 Dept. of Oncology, Karolinska Institute Hospital, Stockholm, Sweden 51 University of Pittsburgh Cancer Institute Laboratory, Pittsburgh, PA, USA 52 National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar 53 Academic Unit of Inflammation and Tumour Targeting, Dept. of Oncology, University of Sheffield Medical School, Sheffield, UK 54 INSERM, UMR1043, Toulouse, France 55 CNRS, UMR5282, Toulouse, France 56 Laboratoire d’Immunologie, CHU Toulouse, Université Toulouse II, Toulouse, France 57 Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Institute, Rozzano, Italy 58 Dept. of Biochemistry, University of Lausanne, Epalinges, Switzerland 59 Dept. of Medical Biotechnologies and Translational Medicine, University of Milan, Rozzano, Italy 60 Dept. of Immunology, Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Spain 61 Dept. of Oncology, Clínica Universidad de Navarra, Pamplona, Spain 62 ISA Therapeutics, Leiden, The Netherlands 63 Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands 64 Research Dept. of Surgical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA 65 Istituto Giannina Gaslini, Genova, Italy 66 Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY, USA 67 Dept. of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA 68 The Jackson Laboratory for Genomics Medicine, Farmington, CT, USA 69 Div. of Hematology/Oncology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA 70 The James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, MD, USA 71 Lankenau Institute for Medical Research, Wynnewood, PA, USA 72 Dept. of Pathology, Anatomy and Cell Biology, Sidney Kimmel Medical College, Philadelphia, PA, USA 73 Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA 74 Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Buenos Aires, Argentina 75 National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA 76 Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, USA 77 Dept. of Pathology, The Cancer Research Center, The University of Chicago, Chicago, IL, USA 78 Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle, Germany 79 Dept. of Immuno-GeneTherapy, Mie University Graduate School of Medicine, Tsu, Japan 80 Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, Portugal 81 Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia 82 School of Medicine, University of Queensland, Herston, Queensland, Australia 83 Dept. of Oncology, University of Lausanne, Lausanne, Switzerland 84 Ludwig Cancer Research Center, Lausanne, Switzerland 85 Dept. of Immunology, University of Connecticut School of Medicine, Farmington, CT, USA 86 Carole and Ray Neag Comprehensive Cancer Center, Farmington, CT, USA 87 Laboratory of Transplantation Immunology, Dept. of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA 88 INSERM, U970, Paris, France 89 Paris-Cardiovascular Research Center (PARCC), Paris, France 90 Service d’Immunologie Biologique, Hôpital Européen Georges Pompidou (HEGP), AP-HP, Paris, France 91 Dept. of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands 92 Ludwig Institute for Cancer Research, Brussels, Belgium 93 de Duve Institute, Brussels, Belgium 94 Université Catholique de Louvain, Brussels, Belgium 95 Dept. of Molecular Medicine and Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA 96 Institute of Medical Microbiology, Immunology and Hygiene, Technical University Munich, Munich, Germany 97 Donald A. Adam Comprehensive Melanoma Research Center, Moffitt Cancer Center, Tampa, FL, USA 98 University of Pittsburgh School of Medicine, Pittsburgh, PA, USA 99 Dept. of Medicine and Ludwig Center, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, USA 100 Weill Cornell Medical College, New York, NY, USA 101 INSERM, U1015, Villejuif, France 102 Centre d’Investigation Clinique Biothérapie 507 (CICBT507), Gustave Roussy Cancer Campus, Villejuif, France 103 University of Michigan, School of Medicine, Ann Arbor, MI, USA 104 Pôle de Biologie, Hôpital Européen Georges Pompidou (HEGP), AP-HP, Paris, France * share senior co-authorship Correspondence: Lorenzo Galluzzi, email: // Keywords : adoptive cell transfer, checkpoint blockers, dendritic cell-based interventions, DNA-based vaccines, immunostimulatory cytokines, peptide-based vaccines, oncolytic viruses, Toll-like receptor agonists Received : November 02, 2014 Accepted : December 15, 2014 Published : December 18, 2014 Abstract During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches.