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AI and Chronic Inflammation
Published in Louis J. Catania, AI for Immunology, 2021
Checkpoint inhibitors are monoclonal antibody drugs that target and attach to PD-1, PD-L1, and CTLA-4, (anti-cancer) proteins on T-cells (and some cancer cells). This binding action can inhibit the proteins and boost the immune response against cancer cells. These drugs are given intravenously and have been shown to be helpful in treating several types of cancer with new cancer types being added as more studies show the drugs to be effective. Examples of drugs that target PD-1 include Pembrolizumab (Keytruda®), Nivolumab (Opdivo®), and Cemiplimab (Libtayo®). PD-L1 drugs include Atezolizumab (Tecentriq®), Avelumab (Bavencio®), and Durvalumab (Imfinzi®). Ipilimumab (Yervoy®) is a CTLA-4 checkpoint inhibitor and is used specifically to treat skin melanoma. Some common side effects of checkpoint inhibitors include diarrhea, pneumonitis (inflammation in the lungs), rashes and itchiness, problems with some hormone levels, and kidney infections.23
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
Currently, immunotherapy is one of the most promising cancer treatments [2] and the development of new immunotherapies has become a necessity [3, 4]. In recent years, immunotherapy has become widespread and has been used to treat both hematological and solid cancers [2]. Immunotherapy is a biological therapy that involves activation of the immune system to target and kill cancer cells through different approaches. Promising immunotherapy approaches include adoptive cell transfer, therapeutic monoclonal antibodies (mAbs), treatment vaccines, cytokine treatment using interferons and interleukins, Bacillus Calmette Guérin (BCG), which is a weakened bacterium used in the treatment of bladder cancer, and immune checkpoint inhibitors. Chimeric antigen receptor therapy also known as CAR T-cell therapy has stood out as a clinically effective type of adoptive cell transfer therapy. Immune checkpoint inhibitors, in particular, have shown potential in the treatment of several cancers and have been FDA approved for the treatment of melanoma (recurrent and/or metastatic), non-small cell lung cancers (NSCLCs), genitourinary cancers (GUCs), head and neck cancers (HNCs), renal cell carcinomas, urothelial carcinomas, non-Hodgkin lymphomas and other cancers [5].
Mechanistic Model of Tumor Response to Immunotherapy
Published in Vittorio Cristini, Eugene J. Koay, Zhihui Wang, An Introduction to Physical Oncology, 2017
Geoffrey V. Martin, Eman Simbawa
In this section, we extend our prior work on modeling chemotherapy to the realm of immunotherapies. We focus on modeling immune checkpoint inhibitor antibodies due to their success in recent clinical trials, although they can be extended to exogenous molecular immunotherapies in general. Briefly, immune checkpoint inhibitors attempt to block the interaction between immune-inhibiting ligands expressed on tumor cells and their binding counterparts on immune cells. Once the tumor ligands are bound to these proteins expressed on the immune cells, they begin a cascade of intracellular events that renders the immune cells ineffective at killing tumor cells. Tumors have a multitude of ways that they can inhibit immune cell killing, but these immune checkpoint pathways represent a prominent mode in some types of cancers. Two of the most clinically relevant immune checkpoint pathways are those associated with cytotoxic T lymphocyte–associated protein-4 (CTLA-4) and PD-1 [343,344]. Blocking the interaction between the tumor ligands specific for CTLA-4 or PD-1 (cluster of differentiation [CD] 80/86 or programmed death ligand-1 [PD-L1], respectively) on immune cells with anti-CTLA4 or anti-PD-1 antibodies has shown clinical responses in colorectal, lung, melanoma, urothelial, and renal cell cancers [293,330,345–347].
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
Tumour immunotherapy is one of the current focuses in oncology. One common form of immunotherapy employs the use of immune checkpoint inhibitors, such as anti-PD-1, in a variety of tumours, including melanoma and lung cancer. A growing number of clinical trials using drugs with this mode of action seek to improve survival rates and quality of life. Current trials suggest that the use of a single agent such as anti-PD-1 produces a low tumour-immune response. Combinations of anti-PD-1 with other types of treatments are the recommended protocol to produce the most effective results (Hamanishi et al., 2016).