Linked Life Data

19679153

Source:http://linkedlifedata.com/resource/pubmed/id/19679153

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2009-10-5
pubmed:abstractText
Immunogenicity of non-human proteins with useful therapeutic properties has prevented their development for use in the therapy of disease. However, this class of proteins could be very useful, if their immunogenicity could be markedly reduced so that many treatment cycles could be administered. One approach to reduce the immunogenicity of foreign proteins is to identify B cell epitopes on the protein and eliminate them by mutagenesis. In this article, theoretical aspects and experimental evidence for the feasibility of B cell epitope removal is reviewed. A special focus is given to our results with deimmunization of recombinant immunotoxins in which Fvs are fused to a 38kDa portion of the bacterial protein, Pseudomonas exotoxin A (PE38). Immunotoxins targeting CD22 and CD25 have produced complete remissions in many patients with drug resistant Hairy Cell Leukemia and are being evaluated in other malignancies. Experimental data summarized in this review indicates that removal of B cell epitopes is a practical approach for making less immunogenic protein therapeutics from non-human functional proteins. This approach requires grouping of the epitopes to identify targets for deimmunization followed by quantitative analysis of the decrease in affinity produced by the mutations in B cell epitopes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1872-8294
pubmed:author
pubmed:issnType
Electronic
pubmed:day
30
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
977-85
pubmed:dateRevised
2010-10-4
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Removal of B cell epitopes as a practical approach for reducing the immunogenicity of foreign protein-based therapeutics.
pubmed:affiliation
Cancer Biology Research Center, Sanford Research/USD, Sioux Falls, SD 57105, USA. nagatas@sanfordhealth.org
pubmed:publicationType
Journal Article, Review, Research Support, N.I.H., Intramural