Journal
IMMUNE NETWORK
Volume 22, Issue 1, Pages -Publisher
KOREA ASSOC IMMUNOLOGISTS
DOI: 10.4110/in.2022.22.e2
Keywords
CTLA-4; PD-1; Immune checkpoint inhibitors; Cancer immunotherapy; Lung cancer
Categories
Funding
- Bio & Medical Technology Development Program of the National Research Foundation - Ministry of Science and ICT [2021R1I1A1A0105744, 2019M3A9B6065231, 2017M3A9E9072669, 2021R1A2C2094629, 2017R1A5A1014560, 2019M3A9B6065221]
- Korea Drug Development Fund - Ministry of Science and ICT, Ministry of Trade, Industry
- Ministry of Health and Welfare [HN21C1410]
- National Research Foundation of Korea [2021R1A2C2094629] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Targeting immune evasion through immune checkpoint pathways has revolutionized cancer treatment. This review discusses the historical discovery of CTLA-4 and PD-1 and their potential as anti-cancer therapeutics. It also explores the clinical utility of immune checkpoint inhibitors, particularly in non-small cell lung cancer, and the ongoing research on combination therapy and novel ICIs.
Targeting immune evasion via immune checkpoint pathways has changed the treatment paradigm in cancer. Since CTLA-4 antibody was first approved in 2011 for treatment of metastatic melanoma, eight immune checkpoint inhibitors (ICIs) centered on PD-1 pathway blockade are approved and currently administered to treat 18 different types of cancers. The first part of the review focuses on the history of CTLA-4 and PD-1 discovery and the preclinical experiments that demonstrated the possibility of anti-CTLA-4 and anti-PD-1 as anti-cancer therapeutics. The approval process of clinical trials and clinical utility of ICIs are described, specifically focusing on non-small cell lung cancer (NSCLC), in which immunotherapies are most actively applied. Additionally, this review covers the combination therapy and novel ICIs currently under investigation in NSCLC. Although ICIs are now key pivotal cancer therapy option in clinical settings, they show inconsistent therapeutic efficacy and limited responsiveness. Thus, newly proposed action mechanism to overcome the limitations of ICIs in a near future are also discussed.
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