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Skip to 0 minutes and 14 seconds Let’s move on to monoclonal antibodies. Let me first clarify that I don’t mean to say monoclonal antibody is a separated category, but rather it is a platform technology. And monoclonal antibodies have important applications. First, in purification technology because given any substance, it is possible to create monoclonal antibodies that specifically bind to that substance, and therefore the monoclonal antibody can be used to detect water purify that substance. It also has diagnostic application when it’s coupled with a radioactive isotope. The monoclonal antibody can target the diseased tissues or cells for diagnosis. And of course importantly, for treatment by itself or coupling with another drug or toxin. And as you have noticed the chemical name of monoclonal antibodies, they all end with MAb.

Skip to 1 minute and 39 seconds Let’s look at some monoclonal antibodies as or used as immunosuppressant.

Skip to 1 minute and 47 seconds For example, there’s two products: Basiliximab, and Daclizumab. They are both carmelized monoclonal antibodies and those are indicated for prophylaxis of the organ rejection after transplantation. And they’re both IL-2 receptor antagonist. Muromonab I mention this for historical reason. Because this is the first monoclonal antibody approved for clinical use in humans for organ transplantation. And it is at 100% marine monoclonal antibody. Okay, the anti-cancer indications for monoclonal antibody. Rituximab, for example, it was approved in 1997, the very first monoclonal antibody to treat cancer. It is a chimeric human marine monoclonal antibody And it is Anti CD20 that is the cancer cells must express CD20 protein on the surface. And it is indicated for non-hodgkins lymphoma.

Skip to 3 minutes and 20 seconds Gemtuzumab Ozogamicin and it is a monoclonal antibody linked to a chemotherapy agent Ozogamicin is a chemotherapeutic agent and it target CD33 and this is used for the treatment of relapse AML which is acute myeloid leukemia. And it was withdrawn in 2011 only after one year on the market because of side effect.

Skip to 4 minutes and 3 seconds Ibritumomab, Tiuxetan, is another monoclonal antibody used for cancer therapy Ibritumomab is an antibody. Tiuxetan is a chelator. To the chelator was attached a radioisotope either yttrium-90 or indium-111. Okay, so the monoclonal antibody is used to bind the CD20 and allowing the radiation from the attached isotope. So this was approved in 2002, the first radio labeled of monoclonal antibody for radioimmunotherapy of the non-hodgkins a new formal. So this is a combination of monoclonal antibody and cheltor to which a radio activity is attached.

Skip to 5 minutes and 20 seconds Yet other anti-cancer monoclonal antibodies, Cetuximab. Okay. It is an epidermal growth factor receptor inhibitor the EGFR inhibitor. It was approved in 2004 for the treatment of metastatic colorectal cancer. But it is only responsive to KRAS wild-type gene or patient Express KRAS wild-type gene but not responsive to the mutant type. And which is about one third of the core rectal cancer patien that is the drug is only what the biologics is only responsive to 2/3 of the colorectal cancer population. The other EGFR inhibitor is Vectibix. And essentially it’s very similar to the Erbitux or the Cetuximab. And therefore it requires genetic screening. Avastin is a VEGF inhibitor.

Skip to 6 minutes and 39 seconds It’s a vascular endothelial growth factor inhibitor and this one does not require a genetic screening.

Skip to 6 minutes and 51 seconds So Trastuzumab or Herceptin. This was approved in 1998 the second monoclonal antibody to treat cancer. The first one was the Trastuzumab as I mentioned earlier for non-hodgkins lymphoma. And it binds to HER2 protein on the surface of the cancer cells. So patients must express HER2 protein to be responsive to Herceptin. It can be used as a monotherapy or in combination with paclitaxel for metastatic breast cancer.

Skip to 7 minutes and 40 seconds This biologics may exhibit receptor mediated metabolism and the dose-dependent kinetics. So there is a potential for overexposure. And these are the packages for Erbitux and for Herceptin.

Monoclonal Antibodies

Monoclonal antibodies (mAb) are antibodies that are made by identical immune cells that are all clones of a unique parent cell. Monoclonal antibodies have monovalent affinity, in that they bind to the same epitope, the part of an antigen that is recognized by the antibody. Because of the antigenic specificity, they can be used for targeted therapy, attacking selective types of cells (e.g., cancer cells) with less harm to normal cells. The naming convention for therapeutic mAbs: the suffix for all mAbs is “mab.”, The infixes designate the target (eg, “ci” for cardiovascular, “so” for bone, “tu” for tumor) and the source (host) in which the antibody was originally produced (eg, “u” for human, “o” for mouse), as well as modifications (eg, “-xi-“ for chimeric, “-zu-“ for humanized).

mAbs are directed against a large number of antigens and used for immunologic diseases, cancer therapy and reversal of drug effects. For example, both Basiliximab and Daclizumab are IL-2 receptor antagonists pharmacologically, but they are made in mAbs for prophylaxis of organ rejection after renal transplant mAb can be used singularly. For example, Rituximab (anti-CD20) was the first approved (1997) MAb to treat non-Hodgkins lymphoma; Trastuzumab (anti-HER2) was the second approved (1998) MAb to treat breast cancer. mAb can be used in combined chemotherapy. For example, Gemtuzumab (anti-CD33) is linked to a chemotherapeutic agent, calicheamicin for the treatment of acute myeloid leukemia (AML). mAb can be used in combined radiation therapy. For example, Ibritumomab (anti- CD20) is attached to a radioactive isotope (yttrium-90 or indium-111). Market growth of global biosimilar MAbs continues amid increasing prevalence of chronic diseases and increase in expiring patents of blockbuster mAbs, and is poised to grow by $ 8.65 bn during 2020-2024.

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Pharmacotherapy: Understanding Biotechnology Products

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