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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.
Delivery of Immune Checkpoint Inhibitors Using Nanoparticles
Published in Hala Gali-Muhtasib, Racha Chouaib, Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
Abdullah Shaito, Houssein Hajj Hassan
Both of the CTLA-4 and the PD-1/PDL-1 immune checkpoints negatively regulate T cell activation yet in different ways. CTLA-4 engages with CD28 and dampens the costimulatory signal already initiated by CD28. Effectively, CTLA-4 puts a brake on activation of T cells already induced by CD28 co-stimulation or, in other words, it can inhibit the already primed T cells. PD-1, on the other hand, acts independent of CD28, and has the ability to directly inhibit activation of T cells. PD-1 can act even on non-primed T cells. Cancer cells can exploit the PD-1/PDL-1 pathway resulting in immunosuppression and T cell exhaustion, and thereby can evade immune anticancer responses. PD-1 or PDL-1 mAbs can disturb this T cell inhibitory signal, leading to reactivation of the anticancer responses of specific CTLs. Moreover, it was demonstrated that targeting CTLA-4, PD-1, or other immune checkpoint molecules can reverse T cell exhaustion and restore T cell functions and activity in chronic viral infections and during cancer [41, 48–53]. The mechanism of action of checkpoint inhibition during cancer immunotherapy is illustrated in Fig. 5.2.
Clinical Management of Pancreatic Cancer
Published in Vittorio Cristini, Eugene J. Koay, Zhihui Wang, An Introduction to Physical Oncology, 2017
Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) serve as key regulators of the immune response, called checkpoints. Activated T-cells express PD-1, while cancer cells and the associated stroma express PD-L1 and PD-L2. Upon binding of PD-1 to one of these ligands, T cells inactivate and undergo apoptosis, allowing tumor immune escape [285,286]. Clinical trials with monoclonal antibodies targeting PD-L1 or PD-1 have shown promising results in several tumors, such as renal cell carcinoma, melanoma, and non-small-cell lung cancer [287]. Although PD-L1 expression has been associated with poor prognosis in PDAC, targeting PD-L1 in PDAC has not shown significant response [286].
Expression of a recombinant anti-programed cell death 1 antibody in the mammary gland of transgenic mice
Published in Preparative Biochemistry & Biotechnology, 2021
Guihua Gong, Wei Zhang, Liping Xie, Lei Xu, Shu Han, Youjia Hu
Programed cell death 1(PD-1) is an inhibitory co-stimulatory receptor expressed on the surface of activated T cells and B cells.[10] The ligand of PD-1, PD-L1, is found to have a high expression level in many human tumors, including melanoma, lung cancer, and kidney. The interaction of PD-1 with PD-L1 limits effector T-cell activity, and therefore downregulates immune responses and autoimmunity. The PD-1/PD-L1 pathway was thought to play a vital role in maintaining an immunosuppressive tumor microenvironment.[11] The blockade of such pathway has been developed as a therapy for a variety types of cancer in clinical use.[12] Nivolumab (Opdivo) is the first approved anti-PD-1 antibody by FDA in 2014 for the treatment of melanoma. As a new targeted immunotherapy, Nivolumab has become one of the most promising approaches for patients with a variety of tumor types.
Nanobodies targeting the interaction interface of programmed death receptor 1 (PD-1)/PD-1 ligand 1 (PD-1/PD-L1)
Published in Preparative Biochemistry & Biotechnology, 2020
Biyan Wen, Lin Zhao, Yuchu Wang, Chuangnan Qiu, Zhimin Xu, Kunling Huang, He Zhu, Zemin Li, Huangjin Li
Programmed cell death protein (PD-1) is a member of the CD28 receptor family expressed on the surface of T cells, T regulatory cells (Tregs) and B cells.[1–3] PD-1 has two major ligands, termed programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). The binding of PD-1 to its ligand inhibits the proliferation and activation of T cells and the secretion of related cytokines. Under normal conditions, PD-1 combined with PD-L1 or PD-L2 inhibits the activation and function of T cells, which in turn upregulates Tregs[4,5] leading to a loss of autoimmunity and enhanced self-tolerance.[6–9] PD-L1 is expressed in normal human tissues and organs but is overexpressed on the surface of various tumor cells. PD-L2 is also been detected in a small number of B-cell lymphomas9.[10] In the normal immune system, the primary role of PD-1/PD-L1 signaling is to maintain the balance of protective immunity and immune tolerance. In the tumor microenvironment, PD-1/PD-L1 signaling prevents effector T cells from identifying and killing tumor cells, resulting in immune cell escape.[1–3]
Tumour-immune dynamics with an immune checkpoint inhibitor
Published in Letters in Biomathematics, 2018
Elpiniki Nikolopoulou, Lauren R. Johnson, Duane Harris, John D. Nagy, Edward C. Stites, Yang Kuang
Two important factors in the tumour-immune response are programmed death-1 (PD-1) and its ligand PD-L1. PD-1 is a protein expressed on activated T cells. PD-L1, found mainly on various types of tumour cells and T cells (Maute et al., 2015; Talay, Shen, Chen, & Chen ,2009), is one of PD-1’s ligands. When PD-1 binds to PD-L1, the PD-1-PD-L1 complex is formed, allowing the cell expressing PD-L1 to be unrecognized as a danger when detected. In response to an immune attack, tumour cells may overexpress PD-L1 and PD-L2 which can bind to PD-1 receptors on T cells, reducing or eliminating the effectiveness of T cells’ attacks (He, Hu, Hu, & Li, 2015).