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Interleukin-2 (IL-2) is an interleukin, a type of cytokine signaling molecule in the immune system. It is a 15.5–16 kDa protein that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible for immunity. IL-2 is part of the body's natural response to microbial infection, and in discriminating between foreign ("non-self") and "self". IL-2 mediates its effects by binding to IL-2 receptors, which are expressed by lymphocytes. The major sources of IL-2 are activated CD4+ T cells and activated CD8+ T cells. Put shortly the function of IL-2 is to stimulate the growth of helper, cytotoxic and regulatory T cells.
Cancer immunotherapy is the stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology.
Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.
Medarex was an American biopharmaceutical company based in Princeton, New Jersey, with manufacturing facilities in Bloomsbury and Annandale, New Jersey, and research facilities in Milpitas and Sunnyvale, California. In 2009, Medarex was purchased by Bristol Myers Squibb.
PEGylation is the process of both covalent and non-covalent attachment or amalgamation of polyethylene glycol polymer chains to molecules and macrostructures, such as a drug, therapeutic protein or vesicle, which is then described as PEGylated. PEGylation affects the resulting derivatives or aggregates interactions, which typically slows down their coalescence and degradation as well as elimination in vivo.
Programmed cell death protein 1, also known as PD-1 and CD279, is a protein on the surface of T and B cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. This prevents autoimmune diseases, but it can also prevent the immune system from killing cancer cells.
Wolfram Samlowski is an American medical oncologist with Comprehensive Cancer Centers of Nevada (CCCN) and a member of the Research Developmental Therapeutics and Genitourinary Committees for US Oncology. His research interests include translational research and development of novel cancer immunotherapy agents, translational drug development as well as gene therapy. His clinical interests are in developing more effective treatments for advanced stages of melanoma and non-melanoma skin cancers, and renal cancer.
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Nivolumab, sold under the brand name Opdivo, is a medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, colon cancer, esophageal squamous cell carcinoma, liver cancer, gastric cancer, and esophageal or gastroesophageal junction (GEJ) cancer. It is used by slow injection into a vein.
Naloxegol is a peripherally acting μ-opioid receptor antagonist developed by AstraZeneca, licensed from Nektar Therapeutics, for the treatment of opioid-induced constipation. It was approved in 2014 in adult patients with chronic, non-cancer pain. Doses of 25 mg were found safe and well tolerated for 52 weeks. When given concomitantly with opioid analgesics, naloxegol reduced constipation-related side effects, while maintaining comparable levels of analgesia.
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Nektar Therapeutics (Nektar) is an American biopharmaceutical company. The company was founded in 1990 and is based in San Francisco, California. The company develops new drug candidates by applying its proprietary PEGylation and advanced polymer conjugate technologies to modify chemical structure of substances. It is a technology supplier to a number of pharmaceutical companies including Affymax, Amgen, Merck, Pfizer and UCB Pharma, etc. The company developed the world's first inhalable non-injectable insulin, Exubera, which was awarded as the bronze award by Wall Street Journal for its technological breakthrough.
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Checkpoint inhibitor therapy is a form of cancer immunotherapy. The therapy targets immune checkpoints, key regulators of the immune system that when stimulated can dampen the immune response to an immunologic stimulus. Some cancers can protect themselves from attack by stimulating immune checkpoint targets. Checkpoint therapy can block inhibitory checkpoints, restoring immune system function. The first anti-cancer drug targeting an immune checkpoint was ipilimumab, a CTLA4 blocker approved in the United States in 2011.
Relatlimab is a monoclonal antibody designed for the treatment of melanoma. It is used in combination with nivolumab to treat melanoma.
Nivolumab/relatlimab, sold under the brand name Opdualag, is a fixed-dose combination medication use to treat melanoma. It contains nivolumab, a programmed death receptor-1 (PD-1) blocking antibody, and relatlimab, a lymphocyte activation gene-3 (LAG-3) blocking antibody. It is given by intravenous infusion.
Cytokines are polypeptides or glycoproteins that help immune cells communicate to each other to induce proliferation, activation, differentiation, and inflammatory or anti-inflammatory signals in various cell types. Studies utilizing cytokines for antitumor therapies has increased significantly since 2000, and different cytokines provide unique antitumor activities. Cytokines hinder tumor cell development mostly through antiproliferative or proapoptotic pathways but can also interrupt development indirectly by eliciting immune cells to have cytotoxic effects against tumor cells. Even though there are FDA-approved cytokine therapies, there are two main challenges associated with cytokine delivery. The first is that cytokines have a short half-life, so frequent administration of high doses is required for therapeutic effect. The second is that systemic toxicity could occur if the cytokines delivered cause an intense immune response, known as a cytokine storm.
References
- ↑ Ekladious I, Colson YL, Grinstaff MW (April 2019). "Polymer-drug conjugate therapeutics: advances, insights and prospects". Nature Reviews. Drug Discovery. 18 (4): 273–294. doi:10.1038/s41573-018-0005-0. PMID 30542076.
- ↑ "Nektar | R&D Pipeline | NKTR-214". Nektar. Retrieved 16 September 2019.
- ↑ "Bempegaldesleukin Plus Nivolumab Granted Breakthrough Designation in Melanoma by the FDA". Targeted Oncology. Retrieved 15 September 2019.
- ↑ Clinical trial number NCT03635983 for "A Study of NKTR-214 Combined With Nivolumab vs Nivolumab Alone in Participants With Previously Untreated Inoperable or Metastatic Melanoma " at ClinicalTrials.gov
- ↑ Clinical trial number NCT03729245 for "A Study of NKTR-214 in Combination With Nivolumab Compared With the Investigator's Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC) " at ClinicalTrials.gov
- ↑ Charych D, Khalili S, Dixit V, Kirk P, Chang T, Langowski J, et al. (5 July 2017). "Modeling the receptor pharmacology, pharmacokinetics, and pharmacodynamics of NKTR-214, a kinetically-controlled interleukin-2 (IL2) receptor agonist for cancer immunotherapy". PLOS One. 12 (7): e0179431. doi: 10.1371/journal.pone.0179431 . PMC 5497954 . PMID 28678791.
- ↑ "Bristol-Myers Squibb and Nektar Therapeutics Announce Global Development & Commercialization Collaboration for Nektar's CD122-biased Agonist, NKTR-214". BMS Newsroom. Bristol-Myers Squibb. Retrieved 16 September 2019.
- ↑ "New Clinical Oncology Collaboration Between Nektar and Pfizer to Evaluate Combination of NKTR-214, a CD122-Biased Agonist, with Avelumab and Talazoparib or Enzalutamide in Multiple Cancers". Nektar Therapeutics. Retrieved 16 September 2019.
- ↑ "Bristol Myers Squibb and Nektar Announce Update on Phase 3 PIVOT IO-001 Trial Evaluating Bempegaldesleukin (BEMPEG) in Combination with Opdivo (nivolumab) in Previously Untreated Unresectable or Metastatic Melanoma". www.businesswire.com. 2022-03-14. Retrieved 2022-03-16.
- ↑ "Nektar Reads Out. Unfortunately". www.science.org. Retrieved 2022-03-16.