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Oncoimmunology. 2015 Mar 2;4(4):e1008814. eCollection 2015 Apr.

Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications.

Author information

1
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.
2
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.
3
Group of Immune receptors of the Innate and Adaptive System, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS) ; Barcelona, Spain.
4
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.
5
Gustave Roussy Cancer Campus ; Villejuif, France.
6
INSERM , U1138; Paris, France ; Equipe 13 , Center de Recherche des Cordeliers ; Paris, France ; Université Pierre et Marie Curie/Paris VI ; Paris, France.
7
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.
8
Sotio a.c. ; Prague, Czech Republic ; Dept. of Immunology, 2nd Faculty of Medicine and University Hospital Motol, Charles University ; Prague, Czech Republic.
9
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.
10
Gustave Roussy Cancer Campus ; Villejuif, France ; INSERM , U1015, CICBT507 ; Villejuif, France.
11
Sotio a.c. ; Prague, Czech Republic ; Equipe 13 , Center de Recherche des Cordeliers ; Paris, France.
12
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.
13
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.
14
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.

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.

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

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