<\/p>\n
<\/p>\n <\/p>\n ADCs comprise an antibody, usually in IgG format,\u00a0conjugated to a cytotoxic drug via a chemical linker.\u00a0The therapeutic concept of ADCs is to use an antibody as a\u00a0vehicle to deliver a cytotoxic drug to a tumor cell by means\u00a0of binding to a target cell surface antigen. ADCs are\u00a0prodrugs requiring drug release for activation, commonly\u00a0after ADC internalization into the target cell. Numerous\u00a0preclinical efficacy studies show that ADCs have significant\u00a0potential for enhancing the antitumor activity of \u201cnaked\u201d\u00a0antibodies and reducing the systemic toxicity of the conjugated drugs.<\/p>\n In order to improve efficacy without compromising safety, an ADC must preferentially\u00a0deliver the cytotoxic payload to tumor cells\u00a0expressing the target antigen rather than to\u00a0healthy tissue. This is accomplished by exploiting the specificity of a mAb targeting an antigen\u00a0that is highly expressed on the surface of malignant cells. After binding the target antigen,\u00a0the ADC-antigen complex is typically internalized and transported to intracellular organelles\u00a0where release of the attached drug can occur.\u00a0Upon release, the cytotoxic drug can interfere with various cellular mechanisms, leading\u00a0to cell death. The development of\u00a0ADCs has relied on several key areas of research\u00a0including the choice of an appropriate antigen\u00a0target, development of novel highly potent cytotoxic drugs, development of stable linkers that\u00a0can release the cytotoxic payload upon internalization, and conjugation technology.<\/p>\n Select an Appropriate Target<\/p>\n Target selection from a candidate\u00a0pool is a critical first step in generating ADCs\u00a0and the most important\u00a0contributor to the antitumor activity and tolerability of an ADC.\u00a0As a general rule, cancer cells\u00a0do not display novel immunogenic antigens\u00a0because such behavior would lead to rapid clearance by the immune system. However, cancer\u00a0cells occasionally express normal cell surface\u00a0antigens at levels that are distinguishable from\u00a0their healthy normal cellular counterparts. Ideally, the target antigen should be expressed with\u00a0substantially higher copy numbers on tumor\u00a0cells, as the efficacy and tolerability of an ADC\u00a0appear to depend, in part, on its relative expression on normal tissue compared to tumor cells.<\/p>\n Linker<\/a><\/p>\n The linker that connects the cytotoxic drug to\u00a0the mAb is a key determinant of ADC activity, including the selectivity, pharmacokinetics, therapeutic index, and overall success of\u00a0the ADC.\u00a0These linkers covalently couple the cytotoxic\u00a0drug to the antibody, producing an ADC that\u00a0should be relatively stable in circulation.<\/p>\n Connection to the antibody<\/p>\n The specific method of attachment of the\u00a0cytotoxic drug and linker to the mAb has been\u00a0shown to play a key role in ADC activity and\u00a0tolerability.\u00a0The two most common naturally occurring amino acids\u00a0that are used to attach the linker drug to\u00a0the antibody are cysteines and lysines.\u00a0The most common methods of\u00a0antibody-drug conjugation are alkylation of reduced interchain disulfides, acylation of lysine\u00a0residues, and alkylation of genetically engineered cysteine residues.<\/p>\n Carter P J, Senter P D. Antibody-drug conjugates for cancer therapy[J]. The Cancer Journal, 2008, 14(3): 154-169.<\/p>\n Sievers E L, Senter P D. Antibody-drug conjugates in cancer therapy[J]. Annual review of medicine, 2013, 64: 15-29.<\/p>\n Flygare J A, Pillow T H, Aristoff P. Antibody-drug conjugates for the treatment of cancer[J]. Chemical biology & drug design, 2013, 81(1): 113-121.<\/p>\n","protected":false},"excerpt":{"rendered":" The concept of arming antibodies by conjugation to\u00a0protein toxins dates back to 1970, and was followed a few\u00a0years later by antibody conjugates with cytotoxic drugs.\u00a0Antibody therapeutics have come of age […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[181],"tags":[430,432,431],"_links":{"self":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/654"}],"collection":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/comments?post=654"}],"version-history":[{"count":2,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/654\/revisions"}],"predecessor-version":[{"id":660,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/654\/revisions\/660"}],"wp:attachment":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/media?parent=654"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/categories?post=654"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/tags?post=654"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}![\"Antibody-Drug-Conjugates-Services-1\"](\"http:\/\/www.bocsci.com\/blog\/wp-content\/uploads\/2017\/06\/Antibody-Drug-Conjugates-Services-1-300x133.jpg\")
<\/a><\/p>\nRelated Products:<\/h4>\n
ADCs Linker \u00a0<\/a><\/h5>\n
ADCs Cytotoxin<\/a><\/h5>\n
ADCs Cytotoxin with Linkers<\/a><\/h5>\n
References:<\/h4>\n