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Role of Nanoparticles in Cancer Immunotherapy
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Immunotherapy mediated by blockade of immunoinhibitory receptors programmed cell death 1 (PD-1) and CTLA-4 that reactivates T cells and clears the antigen/tumor load. Cancer immunotherapy surpassed the contemporary treatment methods in improved survival, efficacy, and applicability to a wide range of tumors irrespective of their origin and type. The beauty of cancer immunotherapy lies in the fact that it not only treats the primary cancer, but can also prevent metastasis and recurrence of the tumor post-treatment. Because of several advantages over other treatment methods, PD-1 blockade-based cancer immunotherapy has led to a paradigm shift in cancer treatment. In 2018, the most prestigious award ‘Nobel Prize’ in ‘Medicine’ for the discovery of PD-1 and CTLA-4 was awarded jointly to Prof. Tasuku Honjo and Prof. J.P. Allison [23]. Summary of the difference between immune checkpoint blockade-based cancer immunotherapy and other standard therapies is given in Table 12.1.
The Precision Medicine Approach in Oncology
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
A study evaluated this assay for its value in supporting the use of pembrolizumab (KeytrudaTM) in patients. This human monoclonal antibody targets the Programmed Cell Death 1 (PD-1) receptor of lymphocytes, and was approved by the FDA in 2017 for the treatment of metastatic melanoma, and any unresectable or metastatic solid tumors with certain genetic anomalies (e.g., mismatch repair deficiency or microsatellite instability). This was the first time that the FDA had approved an anticancer agent based on tumor genetics rather than tissue type or tumor site.
Melanoma-associated emergencies
Published in Biju Vasudevan, Rajesh Verma, Dermatological Emergencies, 2019
Vidya Kharkar, M. R. L. Sujata
Pembrolizumab is a humanized monoclonal IgG4 antibody. It targets human cell surface receptor PD-1 (programmed cell death-1) and interferes with PD-1 ligand binding. This interference results in activation of T-cell-mediated response against tumors. The FDA approved pembrolizumab for the management of advanced or unresectable melanomas that are refractory to other therapeutics.
Vertical level of blood cell division cycle 42 predicts response and survival benefits to PD-1 inhibitor-based regimen in metastatic colorectal cancer patients
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2023
Lili Jiang, Yan Shen, Yixiong Wang
Metastatic colorectal cancer (mCRC) represents a tremendous medical burden in the clinical aspect, accounting for 20% of newly diagnosed colorectal cancer (CRC) cases [1,2]. Due to the occurrence of distal metastasis, most mCRC patients are inoperable and their management options are limited [3]. Programmed cell death-1 (PD-1) inhibitor has been applied in treating various types of solid tumors (such as lung cancer, renal cancer, bladder cancer, etc.) [4]. Inspiringly, recent clinical trials display that PD-1 inhibitor-based regimen also achieves promising tumor response and survival profiles in inoperable mCRC patients [5–7]. However, the objective response rate (ORR) in mCRC patients treated with PD-1 inhibitor-based regimens varies from 31.3% to 43.8%, leaving an unresponsiveness rate above 50% and further impairing their prognosis [8,9]. Hence, it is necessary to identify some potential biomarkers to stratify the inoperable mCRC patients who are beneficial from the PD-1 inhibitor-based regimen before initial therapy and further improve the overall management of inoperable mCRC patients.
Identifying and clinically validating biomarkers for immunotherapy in colorectal cancer
Published in Expert Review of Molecular Diagnostics, 2023
Yung-Sung Yeh, Hsiang-Lin Tsai, Po-Jung Chen, Yen-Cheng Chen, Wei-Chih Su, Tsung-Kun Chang, Ching-Wen Huang, Jaw-Yuan Wang
Programmed cell death-1 (PD-1) and its ligand (PD-L1) are key mediators of immune suppression in a tumor microenvironment. The development of ICIs, such as anti-PD-1, has created a new path for cancer immunotherapy development [41]. In addition to MSI, numerous biomarkers have been discovered and used to guide tumor immunotherapy; they include tumor mutational burden (TMB) [42,43] and PD-L1 expression [44,45]. Because of the role of immune checkpoints in tumor development and immune escape, the use of anti-PD-1/PD-L1 monoclonal antibodies to stimulate an immune response against tumors has become routine clinical practice [46,47]. However, the inhibition of PD-1or PD-L1 therapy has limited effects in CRC treatments. In 2017, the first anti-PD-1 drug, pembrolizumab, was approved by the FDA as a second-line treatment for patients with MSI-H mCRC [18].
Development of neoantigens: from identification in cancer cells to application in cancer vaccines
Published in Expert Review of Vaccines, 2022
Nasim Ebrahimi, Maryam Akbari, Masoud Ghanaatian, Parichehr Roozbahani moghaddam, Samaneh Adelian, Marziyeh Borjian Boroujeni, Elnaz Yazdani, Amirhossein Ahmadi, Michael R. Hamblin
In contrast, RNA molecules coding for neoantigen peptides can also be used as a vaccine platform to target cancer cells in different approach. Due to the general instability of RNA molecules, RNA-based vaccines can cause fewer side effects, show a lower risk of triggering the autoimmune disease, and have a lower probability of integration into the host cell genome compared to DNA-based vaccines [96,97]. Although only a few RNA vaccines have been tested in phase I and II clinical trials, for the first time, Sahin et al. employed a tailored RNA vaccination to treat melanoma. Thirteen patients received RNA vaccination combined with anti-PD-1 checkpoint blockade therapy and showed increased numbers of neoantigen-specific T cells [83]. PD-1 (programmed cell death-1) is an immune checkpoint protein. The expression of PD-1 on the surface of activated T cells, and the expression of its ligands, PD-L1 and PD-L2 on dendritic cells or macrophages, both inhibit the development of T cell responses against tumor cells [98].