title: Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications.
abstract: Immunomodulatory monoclonal antibodies (mAbs) differ from their tumor-targeting counterparts because they exert therapeutic effects by directly interacting with soluble or (most often) cellular components of the immune system. Besides holding promise for the treatment of autoimmune and inflammatory disorders, immunomodulatory mAbs have recently been shown to constitute a potent therapeutic weapon against neoplastic conditions. One class of immunomodulatory mAbs operates by inhibiting safeguard systems that are frequently harnessed by cancer cells to establish immunological tolerance, the so-called "immune checkpoints." No less than 3 checkpoint-blocking mAbs have been approved worldwide for use in oncological indications, 2 of which during the past 12 months. These molecules not only mediate single-agent clinical activity in patients affected by specific neoplasms, but also significantly boost the efficacy of several anticancer chemo-, radio- or immunotherapies. Here, we summarize recent advances in the development of checkpoint-blocking mAbs, as well as of immunomodulatory mAbs with distinct mechanisms of action.
authors.affiliation: Gustave Roussy Cancer Campus ; Villejuif, France ; INSERM , U1138; Paris, France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers ; Paris, France.
authors.forename: Aitziber
authors.initials: A
authors.lastname: Buqué
authors.affiliation: Gustave Roussy Cancer Campus ; Villejuif, France ; INSERM , U1138; Paris, France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers ; Paris, France ; Faculté de Medicine, Université Paris Sud/Paris XI ; Le Kremlin-Bicêtre, France.
authors.forename: Norma
authors.initials: N
authors.lastname: Bloy
authors.affiliation: Group of Immune receptors of the Innate and Adaptive System, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS) ; Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Aranda
authors.affiliation: Gustave Roussy Cancer Campus ; Villejuif, France ; INSERM , U1138; Paris, France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers ; Paris, France ; Faculté de Medicine, Université Paris Sud/Paris XI ; Le Kremlin-Bicêtre, France ; Sotio a.c. ; Prague, Czech Republic.
authors.forename: Francesca
authors.initials: F
authors.lastname: Castoldi
authors.affiliation: Gustave Roussy Cancer Campus ; Villejuif, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Eggermont
authors.affiliation: INSERM , U1138; Paris, France ; Equipe 13 , Center de Recherche des Cordeliers ; Paris, France ; Université Pierre et Marie Curie/Paris VI ; Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cremer
authors.affiliation: INSERM , U1138; Paris, France ; Université Pierre et Marie Curie/Paris VI ; Paris, France ; Dept. of Immunology, 2nd Faculty of Medicine and University Hospital Motol, Charles University ; Prague, Czech Republic.
authors.forename: Wolf Hervé
authors.initials: WH
authors.lastname: Fridman
authors.affiliation: Sotio a.c. ; Prague, Czech Republic ; Dept. of Immunology, 2nd Faculty of Medicine and University Hospital Motol, Charles University ; Prague, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Fucikova
authors.affiliation: INSERM , U1138; Paris, France ; Université Pierre et Marie Curie/Paris VI ; Paris, France ; Laboratory of Integrative Cancer Immunology, Center de Recherche des Cordeliers ; Paris, France ; Université Paris Descartes/Paris V; Sorbonne Paris Cité ; Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Galon
authors.affiliation: Gustave Roussy Cancer Campus ; Villejuif, France ; INSERM , U1015, CICBT507 ; Villejuif, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Marabelle
authors.affiliation: Sotio a.c. ; Prague, Czech Republic ; Equipe 13 , Center de Recherche des Cordeliers ; Paris, France.
authors.forename: Radek
authors.initials: R
authors.lastname: Spisek
authors.affiliation: Université Paris Descartes/Paris V; Sorbonne Paris Cité ; Paris, France ; INSERM , U970; Paris, France ; Paris-Cardiovascular Research Center (PARCC) ; Paris, France ; Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou (HEGP) ; AP-HP; Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Tartour
authors.affiliation: Gustave Roussy Cancer Campus ; Villejuif, France ; INSERM , U1015, CICBT507 ; Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.affiliation: INSERM , U1138; Paris, France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers ; Paris, France ; Université Paris Descartes/Paris V; Sorbonne Paris Cité ; Paris, France ; Pôle de Biologie, Hôpital Européen Georges Pompidou ; AP-HP; Paris, France ; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus ; Villejuif, France.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.affiliation: Gustave Roussy Cancer Campus ; Villejuif, France ; INSERM , U1138; Paris, France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers ; Paris, France ; Université Paris Descartes/Paris V; Sorbonne Paris Cité ; Paris, France.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
keywords: CRC, colorectal carcinoma; CTLA4, cytotoxic T lymphocyte-associated protein 4; FDA, Food and Drug Administration; IL, interleukin; KIR, killer cell immunoglobulin-like receptor; MEDI4736; MPDL3280A; NK, natural killer; NSCLC, non-small cell lung carcinoma; PD-1, programmed cell death 1; RCC, renal cell carcinoma; TGFβ1, transforming growth factor β1; TLR, Toll-like receptor; TNFRSF, tumor necrosis factor receptor superfamily; Treg, regulatory T cell; ipilimumab; mAb, monoclonal antibody; nivolumab; pembrolizumab; urelumab