The evolving landscape of 'next-generation' immune checkpoint inhibitors: A review.
Eur J Cancer
; 117: 14-31, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-31229946
ABSTRACT
'First-generation' immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways ('next-generation' immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Terapia de Alvo Molecular
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Antígeno B7-H1
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Antígeno CTLA-4
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Antineoplásicos Imunológicos
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Imunoterapia
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Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Eur J Cancer
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália