About: The CEA/CD3-Bispecific Antibody MEDI-565 (MT111) Binds a Nonlinear Epitope in the Full-Length but Not a Short Splice Variant of CEA

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About: The CEA/CD3-Bispecific Antibody MEDI-565 (MT111) Binds a Nonlinear Epitope in the Full-Length but Not a Short Splice Variant of CEA Goto Sponge NotDistinct Permalink

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Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	The CEA/CD3-Bispecific Antibody MEDI-565 (MT111) Binds a Nonlinear Epitope in the Full-Length but Not a Short Splice Variant of CEA
Creator	Peng, L Huang, J Brohawn, P Morehouse, C Oberst, M
Source	PMC
abstract	MEDI-565 (also known as MT111) is a bispecific T-cell engager (BiTE®) antibody in development for the treatment of patients with cancers expressing carcinoembryonic antigen (CEA). MEDI-565 binds CEA on cancer cells and CD3 on T cells to induce T-cell mediated killing of cancer cells. To understand the molecular basis of human CEA recognition by MEDI-565 and how polymorphisms and spliced forms of CEA may affect MEDI-565 activity, we mapped the epitope of MEDI-565 on CEA using mutagenesis and homology modeling approaches. We found that MEDI-565 recognized a conformational epitope in the A2 domain comprised of amino acids 326–349 and 388–410, with critical residues F(326), T(328), N(333), V(388), G(389), P(390), E(392), I(408), and N(410). Two non-synonymous single-nucleotide polymorphisms (SNPs) (rs10407503, rs7249230) were identified in the epitope region, but they are found at low homozygosity rates. Searching the National Center for Biotechnology Information GenBank® database, we further identified a single, previously uncharacterized mRNA splice variant of CEA that lacks a portion of the N-terminal domain, the A1 and B1 domains, and a large portion of the A2 domain. Real-time quantitative polymerase chain reaction analysis of multiple cancers showed widespread expression of full-length CEA in these tumors, with less frequent but concordant expression of the CEA splice variant. Because the epitope was largely absent from the CEA splice variant, MEDI-565 did not bind or mediate T-cell killing of cells solely expressing this form of CEA. In addition, the splice variant did not interfere with MEDI-565 binding or activity when co-expressed with full-length CEA. Thus MEDI-565 may broadly target CEA-positive tumors without regard for expression of the short splice variant of CEA. Together our data suggest that MEDI-565 activity will neither be impacted by SNPs nor by a splice variant of CEA.
has issue date	2012-05-04(xsd:dateTime)
bibo:doi	10.1371/journal.pone.0036412
bibo:pmid	22574157
has license	cc-by
sha1sum (hex)	d5a2557d0cb42ffcb93f693d7fa4e70fb817e20b
schema:url	https://doi.org/10.1371/journal.pone.0036412
resource representing a document's title	The CEA/CD3-Bispecific Antibody MEDI-565 (MT111) Binds a Nonlinear Epitope in the Full-Length but Not a Short Splice Variant of CEA
has PubMed Central identifier	PMC3344869
has PubMed identifier	22574157
schema:publication	PLoS One
resource representing a document's body	covid:d5a2557d0cb42ffcb93f693d7fa4e70fb817e20b#body_text
is schema:about of	named entity 'interfere' named entity 'splice variant' named entity 'Real-time' named entity 'CEA' named entity 'MEDI' named entity 'MEDI-565' named entity 'MEDI-565' named entity 'DID' named entity 'TUMORS' named entity '389' named entity 'RECOGNITION' named entity 'PORTION' named entity 'FORMS' named entity 'MEDIATE' named entity 'TARGET' named entity 'ANTIBODY' named entity 'WIDESPREAD' named entity 'AMINO ACIDS' named entity 'DATABASE' named entity 'SUGGEST' named entity 'MUTAGENESIS' named entity 'MULTIPLE' named entity 'SPLICE VARIANT' named entity 'ABSENT' named entity '392' named entity 'RATES' named entity 'NON-' named entity 'THESE' named entity 'PREVIOUSLY' named entity 'FOUND' named entity 'CARCINOEMBRYONIC ANTIGEN' named entity '388' named entity 'POSITIVE' named entity 'ADDITION' named entity 'KILLING' named entity 'MRNA SPLICE VARIANT' named entity 'POLYMERASE CHAIN REACTION ANALYSIS' named entity 'OUR' named entity 'IDENTIFIED' named entity 'MEDIATED' named entity 'KNOWN' named entity 'CEA' named entity 'NONLINEAR' named entity 'BUT' named entity 'LACKS' named entity 'REGION' named entity 'SNPS' named entity 'DID NOT INTERFERE WITH' named entity 'EXPRESSION' named entity '328' named entity '333' named entity 'FORM' named entity 'IS A' named entity 'HOW' named entity 'IMPACTED' named entity 'BUT' named entity 'INDUCE' named entity 'DATA' named entity 'SPLICE VARIANT' named entity 'MT111' named entity 'PATIENTS' named entity 'EPITOPE' named entity 'BINDS' named entity 'BISPECIFIC ANTIBODY' named entity 'SHORT' named entity 'CD3' named entity 'CANCERS' named entity '326' named entity 'N-TERMINAL ' named entity 'MAPPED' named entity 'CEA' named entity 'BINDING' named entity 'AFFECT' named entity 'CRITICAL' named entity 'HUMAN' named entity 'NEITHER' named entity 'LOW'

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