{"id":893,"date":"2020-02-18T11:05:48","date_gmt":"2020-02-18T05:35:48","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=893"},"modified":"2020-02-18T11:05:48","modified_gmt":"2020-02-18T05:35:48","slug":"monoclonal-antibodies","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/monoclonal-antibodies\/","title":{"rendered":"Monoclonal Antibodies"},"content":{"rendered":"\n<p><strong>Monoclonal Antibodies<\/strong><\/p>\n\n\n\n<p><strong><u>Immune system<\/u><\/strong><\/p>\n\n\n\n<ul><li>Protective nature, perception of self vs foreign<\/li><li>Refers to the resistance exhibited by the host towards injury caused by microorganisms and their products.<\/li><li>Innate &amp; Acquired<\/li><li>Active &amp; Passive<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"383\" height=\"314\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-410.png?w=383\" alt=\"\" class=\"wp-image-954\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-410.png 383w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-410-300x246.png 300w\" sizes=\"(max-width: 383px) 100vw, 383px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"322\" height=\"293\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-411.png?w=322\" alt=\"\" class=\"wp-image-955\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-411.png 322w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-411-300x273.png 300w\" sizes=\"(max-width: 322px) 100vw, 322px\" \/><\/figure>\n\n\n\n<p>In 1986 \u2013 1st monoclonal antibody(OKT-3\/muromonab CD3) produced &amp; approved for use of organ transplant rejection<\/p>\n\n\n\n<p><img loading=\"lazy\" decoding=\"async\" width=\"454\" height=\"369\" src=\"\"><strong>Hybridoma Technology &amp; Production<\/strong><\/p>\n\n\n\n<ul><li>Identify surface receptors &nbsp;&nbsp;associated with major cancers<\/li><\/ul>\n\n\n\n<ul><li>Search genome databases for genes regulating receptors<\/li><\/ul>\n\n\n\n<ul><li>Compare gene sequences to that of living cancer cells<\/li><\/ul>\n\n\n\n<ul><li>Use microarrays to find genes active in cancer but not in normal cells<\/li><\/ul>\n\n\n\n<ul><li>Identify target receptor proteins<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"454\" height=\"369\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-412.png?w=454\" alt=\"\" class=\"wp-image-956\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-412.png 454w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-412-300x244.png 300w\" sizes=\"(max-width: 454px) 100vw, 454px\" \/><\/figure>\n\n\n\n<ul><li><strong>Other methods<\/strong><ul><li>Transgenic mice \u2013 the embryonic stem cell method \u2013 making \u201cknocked out\u201d antibodies<\/li><\/ul><ul><li>Phase display<\/li><\/ul><\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"421\" height=\"354\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-413.png?w=421\" alt=\"\" class=\"wp-image-957\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-413.png 421w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-413-300x252.png 300w\" sizes=\"(max-width: 421px) 100vw, 421px\" \/><\/figure>\n\n\n\n<p><img loading=\"lazy\" decoding=\"async\" width=\"372\" height=\"287\" src=\"\"><strong><u>Types of Monoclonal Ab<\/u><\/strong><\/p>\n\n\n\n<ul><li>First generation mAB<ul><li>Murine Antibodies \u2013 derived from rat, rabbit etc.<\/li><\/ul><\/li><li>Second generation mAB<ul><li>Chimeric AB \u2013\u00a0\u00a0\u00a0 Infliximab, Rituximab, Abciximab<\/li><\/ul><ul><li>Humanized AB \u2013 Daclizumab, Vitaxin, Herceptin<\/li><\/ul><ul><li>Primatized AB<\/li><\/ul><\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"372\" height=\"286\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-414.png?w=372\" alt=\"\" class=\"wp-image-959\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-414.png 372w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-414-300x231.png 300w\" sizes=\"(max-width: 372px) 100vw, 372px\" \/><\/figure>\n\n\n\n<p><strong><u>Other Classification of MAbs<\/u><\/strong><\/p>\n\n\n\n<ul><li>Naked Mabs \u2013 with out any drug or radioactive material attached to them<\/li><\/ul>\n\n\n\n<p>\u00a0&#8211; e. g. Transtuzumab, Rituximab, Cituximab<\/p>\n\n\n\n<ul><li>Conjugated\/Tagged\/Labeled\/Loaded Mabs<\/li><\/ul>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &#8211; with radioactive particle<\/p>\n\n\n\n<p>\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 &#8211; e.g. Ibritummomab tiuxetan \u2013 for B-cell NHL<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"680\" height=\"396\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-415.png?w=680\" alt=\"\" class=\"wp-image-960\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-415.png 680w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-415-300x175.png 300w\" sizes=\"(max-width: 680px) 100vw, 680px\" \/><\/figure>\n\n\n\n<p><strong>Mechanism of Action of MAbs<\/strong><img loading=\"lazy\" decoding=\"async\" width=\"339\" height=\"299\" src=\"\"><\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"339\" height=\"298\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-416.png?w=339\" alt=\"\" class=\"wp-image-961\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-416.png 339w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-416-300x264.png 300w\" sizes=\"(max-width: 339px) 100vw, 339px\" \/><\/figure>\n\n\n\n<p><strong>Blocking of the function of target antigen<\/strong> i.e. T-lymphocytes, B-lymphocytes, TNF alpha and Interleukin<\/p>\n\n\n\n<p><strong>Cytotoxicity to the cell expressing target antigen<\/strong> by ADCC or CDC<\/p>\n\n\n\n<p><strong>Inhibition of growth factors like EGF<\/strong> e.g. Cetuximab act as EGFR inhibitor<\/p>\n\n\n\n<p><strong>Pharmacokinetic<\/strong><\/p>\n\n\n\n<p><strong>A.&nbsp; Antibody Absorption<br><\/strong>Intravenous (IV) administration<\/p>\n\n\n\n<p>Some extravascular administration<br>Subcutaneous (SC) administration &#8211;&nbsp; Adalimumab, Efalizumab, Omalizumab<br><br>Intramuscular (IM) administration &#8211;&nbsp; Palivizumab<br>&nbsp;<br>Intravitreal administration&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &#8211;&nbsp; Ranibizumab, (Bevacizumab \u2013off label drug)<\/p>\n\n\n\n<p><strong>B. ANTIBODY DISTRIBUTION:<\/strong><\/p>\n\n\n\n<p>MABs, diffuse across vascular endothelial cells very slowly, as they are <strong>polar.<\/strong><\/p>\n\n\n\n<p><strong>Higher concentrations are observed in tissues with leaky vasculature<\/strong> (e.g., bone marrow and spleen)<\/p>\n\n\n\n<p>IgG antibodies show <strong>very little distribution to the brain.<\/strong><\/p>\n\n\n\n<p><strong>C. ANTIBODY ELIMINATION<\/strong><\/p>\n\n\n\n<p>Dose-dependent elimination (e.g., trastuzumab, rituximab, gemtuzumab, and panitumumab)<\/p>\n\n\n\n<p>Elimination of large immune complexes may follow the <strong>nonlinear elimination kinetics<\/strong> (omalizumab, which is thought to interact with soluble target IgE)<\/p>\n\n\n\n<p>Target-meditated elimination is capacity limited (saturable) because of finite expression of the target.<\/p>\n\n\n\n<p>Dose, the expression level of the target, a function of the kinetics of receptor internalization and intracellular catabolism.<\/p>\n\n\n\n<p><strong>MOA for adverse effects :<\/strong><\/p>\n\n\n\n<p>Xenogenetic nature of MAbs<\/p>\n\n\n\n<p>Suppressions of physiological function<\/p>\n\n\n\n<p>Activation of inflammatory cell and mediators<\/p>\n\n\n\n<p>Allergic reactions (due to massive cytokines release) &#8211; Skin rashes<\/p>\n\n\n\n<ul><li>Flu like symptoms \u2013 chills, fatigue, fever, muscle ache &amp; pain<\/li><li>Nausea &amp; Diarrhea<\/li><li>Infusion reaction<\/li><li>Bone marrow depression \u2013 leucopenia, thrombocytopenia &amp; anemia<\/li><li>Increased risk of infection and cancer development<\/li><li>Reactivation of Tuberculosis<\/li><li>hypogammaglobulinemia<\/li><\/ul>\n\n\n\n<p><strong>Uses:<\/strong><\/p>\n\n\n\n<ol type=\"1\"><li><strong><u>Immune mediated disease<\/u><\/strong><\/li><li>Graft rejection<\/li><li>Inflammatory bowel disease \u2013 CD, UC<\/li><li>&nbsp;RA, PSA, AS, SLE, CAPS<\/li><li>Asthma<\/li><li>Psoriasis<\/li><li><strong><u>Hematological malignancies and solid tumors<\/u><\/strong><\/li><li>NHL, CLL, Colorectal Ca, HNC, Breast Ca<\/li><\/ol>\n\n\n\n<ol type=\"1\" start=\"3\"><li><strong>&nbsp;<u>Angiogenesis inhibitors<\/u><\/strong><\/li><li><strong><u>Antiplatelet<\/u><\/strong><\/li><li><strong><u>Diagnostic uses<\/u><\/strong><\/li><li>CEA-Scan<\/li><li>Myoscint<\/li><li>Verluma<\/li><li>ProstaScint<\/li><\/ol>\n\n\n\n<ol type=\"1\" start=\"6\"><li><strong><u>Grouping blood types and identifying viruses<\/u><\/strong><\/li><li><img loading=\"lazy\" decoding=\"async\" width=\"357\" height=\"322\" src=\"\"><img loading=\"lazy\" decoding=\"async\" width=\"364\" height=\"317\" src=\"\"><strong><u>&nbsp;Purification of proteins and drugs<\/u><\/strong><\/li><\/ol>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"364\" height=\"317\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-417.png?w=364\" alt=\"\" class=\"wp-image-962\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-417.png 364w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-417-300x261.png 300w\" sizes=\"(max-width: 364px) 100vw, 364px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"357\" height=\"322\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-418.png?w=357\" alt=\"\" class=\"wp-image-963\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-418.png 357w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-418-300x271.png 300w\" sizes=\"(max-width: 357px) 100vw, 357px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"316\" height=\"360\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-419.png?w=316\" alt=\"\" class=\"wp-image-964\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-419.png 316w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-419-263x300.png 263w\" sizes=\"(max-width: 316px) 100vw, 316px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"379\" height=\"216\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-420.png?w=379\" alt=\"\" class=\"wp-image-965\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-420.png 379w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-420-300x171.png 300w\" sizes=\"(max-width: 379px) 100vw, 379px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"373\" height=\"327\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-421.png?w=373\" alt=\"\" class=\"wp-image-966\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-421.png 373w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-421-300x263.png 300w\" sizes=\"(max-width: 373px) 100vw, 373px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"417\" height=\"360\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-422.png?w=417\" alt=\"\" class=\"wp-image-967\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-422.png 417w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-422-300x259.png 300w\" sizes=\"(max-width: 417px) 100vw, 417px\" \/><\/figure>\n\n\n\n<ul><li><strong><u>Diagnostic uses<\/u><\/strong><ul><li>CEA-Scan \u2013&nbsp; Arcitumomab linked to Tc 99m for colon &amp; rectal cancer<\/li><\/ul><ul><li>Myoscint&nbsp; \u2013&nbsp;&nbsp; Imcriromab linked to Indium(111 In), for MI<\/li><\/ul><ul><li>Verluma&nbsp; \u2013&nbsp;&nbsp;&nbsp; Nofetumomab linked to Tc 99m, for SCLC<\/li><\/ul><ul><li>ProstaScint \u2013 Capromab Pendetide linked Indium (111m In) for prostate cancer<\/li><\/ul><ul><li>Other uses<\/li><\/ul><ul><li>&nbsp;Grouping blood types and identifying viruses<\/li><\/ul><ul><li>&nbsp;Purification of proteins and drugs<\/li><\/ul><\/li><\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Monoclonal Antibodies Immune system Protective nature, perception of self vs foreign Refers to the resistance exhibited by the host towards injury caused by microorganisms and their products. Innate &amp; Acquired Active &amp; Passive In 1986 \u2013 1st monoclonal antibody(OKT-3\/muromonab CD3) produced &amp; approved for use of organ transplant rejection Hybridoma Technology &amp; Production Identify surface[&#8230;]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/893"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=893"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/893\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=893"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=893"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=893"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}