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Keywords = Yervoy® (ipilimumab)

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53 pages, 2354 KiB  
Review
Negative Immune Checkpoint Inhibitors
by Magda Drewniak-Świtalska, Paulina Fortuna and Małgorzata Krzystek-Korpacka
Pharmaceutics 2025, 17(6), 713; https://doi.org/10.3390/pharmaceutics17060713 - 28 May 2025
Cited by 1 | Viewed by 1203
Abstract
Checkpoint inhibitors are a modern therapeutic approach for treating various types of cancer, metabolic diseases, and chronic infections. The main goal of this therapy is to specifically unlock the immune system, allowing it to recognize and eliminate cancer cells or pathogens, primarily through [...] Read more.
Checkpoint inhibitors are a modern therapeutic approach for treating various types of cancer, metabolic diseases, and chronic infections. The main goal of this therapy is to specifically unlock the immune system, allowing it to recognize and eliminate cancer cells or pathogens, primarily through the activation of T lymphocytes. Monoclonal antibodies used in the treatment of various cancers, such as pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy), carry several limitations, primarily due to their large molecular size. The main challenges include limited tissue penetration, long half-life in the body, and the risk of autoimmune responses. Compared to antibodies, small-molecule and peptide inhibitors offer significant advantages related to their molecular structure. These drugs demonstrate a better ability to penetrate hard-to-reach areas, such as the tumor microenvironments, can be administered orally, and often show lower immunogenicity. A new generation of drugs is PROTACs, which combine the ability to direct proteins to degradation with the action of checkpoint inhibitors, contributing to the elimination of proteins responsible for suppressing the immune response. This publication describes small-molecule inhibitors, peptide inhibitors, and PROTAC molecules targeting negative immune checkpoints—CTLA-4, PD-1, VISTA, TIM-3, BTLA-4, LAG-3, and TIGIT. Full article
(This article belongs to the Section Drug Targeting and Design)
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13 pages, 1585 KiB  
Review
Perimyocarditis Associated with Immune Checkpoint Inhibitors: A Case Report and Review of the Literature
by Walid Shalata, Rachel Steckbeck, Amjad Abu Salman, Omar Abu Saleh, Ashraf Abu Jama, Zoé Gabrielle Attal, Sondos Shalata, Hilmi Alnsasra and Alexander Yakobson
Medicina 2024, 60(2), 224; https://doi.org/10.3390/medicina60020224 - 28 Jan 2024
Cited by 2 | Viewed by 3015
Abstract
Patient prognoses have been significantly enhanced by immune checkpoint inhibitors (ICIs), altering the standard of care in cancer treatment. These novel antibodies have become a mainstay of care for metastatic non-small-cell lung cancer (mNSCLC) patients. Several types of adverse events related to ICIs [...] Read more.
Patient prognoses have been significantly enhanced by immune checkpoint inhibitors (ICIs), altering the standard of care in cancer treatment. These novel antibodies have become a mainstay of care for metastatic non-small-cell lung cancer (mNSCLC) patients. Several types of adverse events related to ICIs have been identified and documented as a result of the launch of these innovative medicines. We present here a 74-year-old female patient with a stage IV lung adenocarcinoma, treated with nivolumab plus ipilimumab, who developed perimyocarditis two weeks after receiving the third cycle of immune checkpoint inhibitor therapy. The patient was diagnosed using troponin levels, computed tomography (CT) angiography, and echocardiography. After hospitalization, her cardiac condition was successfully resolved with corticosteroids, colchicine, and symptomatic treatment. To the best of our knowledge, this is one of the rarest cases to be reported of perimyocarditis as a toxicity of immunotherapy in a patient treated for adenocarcinoma of the lung. Full article
(This article belongs to the Special Issue Innovations in the Field of Cardio-Oncology)
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16 pages, 4336 KiB  
Review
Molecular Interactions of Antibody Drugs Targeting PD-1, PD-L1, and CTLA-4 in Immuno-Oncology
by Hyun Tae Lee, Sang Hyung Lee and Yong-Seok Heo
Molecules 2019, 24(6), 1190; https://doi.org/10.3390/molecules24061190 - 26 Mar 2019
Cited by 205 | Viewed by 20340
Abstract
Cancer cells can evade immune surveillance through the molecular interactions of immune checkpoint proteins, including programmed death 1 (PD-1), PD-L1, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Since 2011, the FDA-approved antibody drugs ipilimumab (Yervoy®), nivolumab (Opdivo®), pembrolizumab (Keytruda [...] Read more.
Cancer cells can evade immune surveillance through the molecular interactions of immune checkpoint proteins, including programmed death 1 (PD-1), PD-L1, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Since 2011, the FDA-approved antibody drugs ipilimumab (Yervoy®), nivolumab (Opdivo®), pembrolizumab (Keytruda®), cemiplimab (Libtayo®), atezolizumab (Tecentriq®), durvalumab (Imfinzi®), and avelumab (Bavencio®), which block the immune checkpoint proteins, have brought about a significant breakthrough in the treatment of a wide range of cancers, as they can induce durable therapeutic responses. In recent years, crystal structures of the antibodies against PD-1, PD-L1, and CTLA-4 have been reported. In this review, we describe the latest structural studies of these monoclonal antibodies and their interactions with the immune checkpoint proteins. A comprehensive analysis of the interactions of these immune checkpoint blockers can provide a better understanding of their therapeutic mechanisms of action. The accumulation of these structural studies would provide a basis that is essential for the rational design of next-generation therapies in immuno-oncology. Full article
(This article belongs to the Special Issue Frontier of Protein Crystallography)
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