Trial watch: Immune checkpoint blockers for cancer therapy

Claire Vanpouille-Box

Claire Lhuillier

Lucillia Bezu

Fernando Aranda

Sandra Demaria+4 authors

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^{Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA}

^{Université Paris Descartes/Paris V, Paris, France}

^{Université Pierre et Marie Curie/Paris VI, Paris, France}

^{Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France}

^{INSERM, U1138, Paris, France}

^{Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France}

^{Immunoreceptors of the Innate and Adaptive System Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain}

^{Sotio a.c., Prague, Czech Republic}

^{Dept. of Immunology, 2nd Faculty of Medicine and University Hospital Motol, Charles University, Prague, Czech Republic}

^{Sandra and Edward Meyer Cancer Center, New York, NY, USA}

^{Gustave Roussy Comprehensive Cancer Institute, Villejuif, France}

^{INSERM, U1015, Villejuif, France}

^{Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France}

^{Université Paris Sud/Paris XI, Le Kremlin-Bicêtre, France}

^{Department of Women's and Children's Health, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden}

^{Pôle de Biologie, Hopitâl Européen George Pompidou, AP-HP, Paris, France}

CONTACT Dr. Lorenzo Galluzzi ti.enofadov@codaed, Weill Cornell Medical College, Department of Radiation Oncology, 525 East 68th Street, Box # 169, New York, NY 10065, USA

Supplemental data for this article can be accessed on the publisher's website.

^{Equally contributed.}

Supplemental data for this article can be accessed on the publisher's website.

Received 2017 Aug 23; Accepted 2017 Aug 25.

ABSTRACT

Immune checkpoint blockers (ICBs) are literally revolutionizing the clinical management of an ever more diversified panel of oncological indications. Although considerable attention persists around the inhibition of cytotoxic T lymphocyte-associated protein 4 (CTLA4) and programmed cell death 1 (PDCD1, best known as PD-1) signaling, several other co-inhibitory T-cell receptors are being evaluated as potential targets for the development of novel ICBs. Moreover, substantial efforts are being devoted to the identification of biomarkers that reliably predict the likelihood of each patient to obtain clinical benefits from ICBs in the absence of severe toxicity. Tailoring the delivery of specific ICBs or combinations thereof to selected patient populations in the context of precision medicine programs constitutes indeed a major objective of the future of ICB-based immunotherapy. Here, we discuss recent preclinical and clinical advances on the development of ICBs for oncological indications.

KEYWORDS: Atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab, pembrolizumab

ABSTRACT

Abbreviations: dMMR, mismatch repair deficient; FDA, Food and Drug Administration; ICB, immune checkpoint blocker; MSI-H, microsatellite instability-high; NSCLC, non-small cell lung carcinoma; SCCHN, squamous cell carcinoma of the head and neck.

Abbreviations: GIST, gastrointestinal stromal tumor; HCC, hepatocellular carcinoma; HNSCC, head and neck squamous cell carcinoma; ICB, immune checkpoint blocker; MCC, Merkel cell carcinoma; n.a., not available; NSCLC, non-small cell lung carcinoma; peg-IFNα-2b, pegylated interferon α-2b; RCC, renal cell carcinoma; SCLC, small cell lung cancer; T-VEC, talimogene laherparepvec.

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