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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2018

Open Access 01-12-2018 | Review

Next generation of immune checkpoint therapy in cancer: new developments and challenges

Authors: Julian A. Marin-Acevedo, Bhagirathbhai Dholaria, Aixa E. Soyano, Keith L. Knutson, Saranya Chumsri, Yanyan Lou

Published in: Journal of Hematology & Oncology | Issue 1/2018

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Abstract

Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body’s immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways. Drugs blocking these pathways are currently utilized for a wide variety of malignancies and have demonstrated durable clinical activities in a subset of cancer patients. This approach is rapidly extending beyond CTLA-4 and PD-1/PD-L1. New inhibitory pathways are under investigation, and drugs blocking LAG-3, TIM-3, TIGIT, VISTA, or B7/H3 are being investigated. Furthermore, agonists of stimulatory checkpoint pathways such as OX40, ICOS, GITR, 4-1BB, CD40, or molecules targeting tumor microenvironment components like IDO or TLR are under investigation. In this article, we have provided a comprehensive review of immune checkpoint pathways involved in cancer immunotherapy, and discuss their mechanisms and the therapeutic interventions currently under investigation in phase I/II clinical trials. We also reviewed the limitations, toxicities, and challenges and outline the possible future research directions.
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Metadata
Title
Next generation of immune checkpoint therapy in cancer: new developments and challenges
Authors
Julian A. Marin-Acevedo
Bhagirathbhai Dholaria
Aixa E. Soyano
Keith L. Knutson
Saranya Chumsri
Yanyan Lou
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2018
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-018-0582-8

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