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Therapeutic Applications of Monoclonal Antibodies

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This is a brief introduction to some of the therapeutic applications of monoclonal antibodies. Design inspired by Salman Khan. Special thanks to Professor DeMasi @ MCPHS University.

Hello and welcome back in this video we’ll be talking about the therapeutic applications of monoclonal antibodies in general monoclonal antibody treatments carry fewer side effects than do normal treatments because monoclonal antibodies have a higher degree of specificity and those off site therapeutic activities are less likely to occur if you can recall from the

Last video on monoclonal antibody production i said that there were four types of ma b’s murine chimeric humanized and fully human which are basically ma b’s that are derived from human plasma b-cells rather than mouse b-cells remember during ma b’s are derived from mice chimeric and human eyes are both derived from transgenic mice chimeric ma bees have mirroring

Variable regions and human constant regions while humanized ma bees are mostly human except the complementarity determining regions or cdr also known as hypervariable regions these cdrs are mirroring derive now we have a nomenclature for mep drugs that will help us differentiate all four types and here they are mirian monoclonal antibodies are indicated by the suffix

O map and it’s important to note that these mouse antibodies are essentially form proteins which can trigger the formation of anti mouse human antibodies which is the main reason behind its low efficacy chimeric monoclonal antibodies are indicated by their suffix c map and remember chimeric monoclonal antibodies have mirroring variable regions with human constant

Regions humanized monoclonal antibodies are indicated by the suffix zum ab and they are almost entirely of human origin with the exception of their complementarity determining regions or hypervariable regions these regions are mirroring derived and lastly fully human monoclonal antibodies are indicated by the suffix mum ab and these are a little more difficult to

Build but they are entirely of human origin which includes constant regions variable regions and the complementarity determining regions so there are entirely of human origin in the first introduction video we talked about muramana and how it was news to tree transplant rejection although it was the first of its kind ramen ab and other mirin derived monoclonal

Antibodies had low efficacy since our bodies will tend to create antibodies against these mouse proteins which resulted in side-effects that’s why scientists have shifted their focus on the other three types of monoclonal antibodies and clinical development of mearing drugs decreased drastically until a job to virtually zero in 2003 interestingly the first fully

Human monoclonal antibody drug was launched in 2003 as well and it was called adalimumab with the trade name humira humera targets the protein tumor necrosis factor or tnf which is a cytokine that is secreted mainly by macrophages to induce local inflammation which causes dilation of blood vessels and facilitates in the recruitment of natural killer cells this

Is a good thing when we have an infection but it can cause some problems if we have too much tnf especially when there’s no infection so over production of tnf can lead to autoimmune disorders such as rheumatoid arthritis which is the information of the joints in the fingers wrists feet and ankles this may result in excruciating joint deformity and humira works

By blocking the or neutralizing the excess of tnf proteins from attaching to healthy cells thereby reducing the damaging effects of the excess tnf in 1994 the first chimeric monoclonal antibody drug was approved and it was called abscissa mab with a trade name rio pro rio pearl binds to the intact platelet receptors that are involved in platelet aggregation which

Prevents coagulation rio pro is considered a blood thinner that helps prevent thrombosis and myocardial ischemia which occurs when blood flow is blocked by plaque an example of a humanized monoclonal antibody is o’malley’s lab also known as its trade name solaire and this drug inhibits the binding of ige to the fc epsilon receptor on the surface of mast cells

Two fills and eosinophils solar binds to free ige to interrupt the allergic implement or a cascade of asthma remember that ige fc e epsilon receptor complex when bound to an antigen will activate the degranulation of granulocytes releasing inflammatory mediators such as histamine monoclonal antibodies are also used in cancer treatments they help combat cancerous

Growth through many functions that include opsonization initiating a pentose asst blocking growth signals preventing angiogenesis or development of new blood vessels and they also deliver radiation to specific locations now let’s take a look an example of each of these functions number one monoclonal antibodies that make the cancer cells more visible to the immune

System the drug rituximab tradename rituxan is an fda-approved monoclonal antibody that treats chronic lymphocytic leukemia and non-hodgkins lymphoma and you can tell it’s a chimeric monoclonal antibody by a suffix submit’ rituximab works by targeting and binding tightly to a specific protein called cd20 which is found on both normal and malignant b cells when

Rituximab attaches to this protein cd20 on the b cells it makes it cells more visible to an immune system which can then attack this is called antibody dependent cell-mediated cytotoxicity or adcc the binding of the antibody leads to the classical pathway of complement activation which recruits complement proteins to punch holes in the cell membrane via membrane

Attack complex and this floods the cell and leads to the cell lysis this is also known as complement dependent cytotoxicity or cdc binding of this antibody signals the cell to self-destruct which is also known as a mitosis the primary function of rituximab is to lower the number of b-cells in your system which includes your own healthy b cells however your body

Will produce new healthy b cells to replace these so ultimately the cancerous b cells are less likely to recur number two model cloning two bodies that block growth signals the jokes at talks about tradename erbitux is an fda-approved chimeric monoclonal antibody that treats colon cancer and head and neck cancers so tucks amman works by inhibiting epidermal growth

Factor receptors egfr found on cancerous cells chemical growth factors would be unable to detach these receptors those that signal to grow is not generated cancer cells and some healthy cells rely on this signal to tell them to divide and multiply by blocking the signal from reaching its target so toxin may slow or stop the cancer from growing number three monoclonal

Antibodies that stop new blood vessels from forming the drug bevacizumab tradename avastin is a humanized monoclonal that is fda-approved to treat brain colon kidney and lung cancers tumor cells rely on blood vessels to bring them the oxygen and the nutrients they need to grow and propagate to attract blood vessels cancer cells released a protein vascular endothelial

Growth factor or vegf avastin works by binding to the e v gf protein which blocks the tumors ability to communicate with nearby blood vessels thus interfering with the tumors ability to grow in the case of a tumor with a already established network of blood vessels blocking the growth signals could cause the blood vessel to die and the tumor to shrink number four

Monoclonal antibodies that deliver radiation to cancer cells the drug ibrahim ahmad trade names evelyn is a mirroring conjugated monoclonal antibody that is fda approved to treat non-hodgkins lymphoma which are cancers of white blood cells in the absence of red sternberg cells ebury tumor map is an igg antibody in conjunction with an isotope either atrium ninety

Or indium 111 this monoclonal antibody works by binding to the cd20 antigen found on malignant b cells allowing radiation from the attached isotope to kill the b-cells also similar to rituximab which binds to the same cd20 antigen ebury tumor map can trigger cell death via a dcc antibody dependent cell-mediated cytotoxicity or cdc complement dependent cytotoxicity

And a patos asst researchers believe that this multi effector mechanism is as effective as the more conventional high-dose external beam radiation as you can see monoclonal antibodies can be used in many applications ranging from ordering therapy’s to cancer treatments and unlike most drugs which can have major side effects monoclonal antibody drugs harnesses the

Power of our adaptive immune system to treat the disease and because they are highly specific ma b’s have greater therapeutic revelon and less side effects so i hope you found this video to be useful for more information on the therapeutic applications of ma b’s please visit the websites listed in the description below and as always thank you for watching

Transcribed from video
Therapeutic Applications of Monoclonal Antibodies By John Nguyen