In silico strategy for detection of target candidates for antibody therapy of solid tumors.
In contrast to earlier attempts for the identification of target candidates suitable for monoclonal antibody (mAb) based cancer therapies we concentrated on highly selective lineage-specific genes additionally preserved or even overexpressed in orthotopic cancers. In a script aided workflow we reduced all human entries of the RefSeq mRNA database to those encoding transmembrane domain bearing gene products and subjected them to BLAST analysis against the human EST database. All BLAST results were validated in a gene centric way allowing two types of data curation prior to expression profiling of matching ESTs in selected healthy tissues: (i) exclusion of questionable ESTs arising e.g. from genomic contamination and (ii) elimination of erroneously predicted mRNAs as well as transcripts with only weak EST coverage. The impact of such stringent input control on accuracy of prediction is underlined by RT-PCR confirmation of predicted tissue distribution patterns for a number of selected candidates.
Helftenbein
Gerd
G
Ganymed Pharmaceuticals AG, Mainz, Germany.
Koslowski
Michael
M
Dhaene
Karl
K
Seitz
Gerhard
G
Sahin
Ugur
U
Türeci
Ozlem
O
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019295:Computational Biology; D016208:Databases, Factual; D020224:Expressed Sequence Tags; D005796:Genes / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D012333:RNA, Messenger