RGD Reference Report - Human monoclonal antibodies to domain C of tenascin-C selectively target solid tumors in vivo. - Rat Genome Database

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Human monoclonal antibodies to domain C of tenascin-C selectively target solid tumors in vivo.

Authors: Silacci, M  Brack, SS  Spath, N  Buck, A  Hillinger, S  Arni, S  Weder, W  Zardi, L  Neri, D 
Citation: Silacci M, etal., Protein Eng Des Sel. 2006 Oct;19(10):471-8. Epub 2006 Aug 22.
RGD ID: 4889612
Pubmed: PMID:16928692   (View Abstract at PubMed)
DOI: DOI:10.1093/protein/gzl033   (Journal Full-text)

We had previously reported that splice isoforms of tenascin-C containing the extra-domain C are virtually absent in normal adult tissues but are highly abundant in high-grade astrocytomas, with a prominent peri-vascular pattern of expression. We now report that the extra-domain C of tenascin-C is strongly expressed in the majority of lung cancers, with a vascular and stromal pattern of expression. Using antibody phage technology, we have generated a human monoclonal antibody (G11), with a dissociation constant K(D) = 4.2 nM for the human domain C. The G11 antibody, expressed in scFv and in mini-antibody (SIP) format, as well as a scFv-interleukin-2 fusion protein, was then characterized in quantitative biodistribution studies using mice grafted subcutaneously with U87 gliomas, revealing a selective tumor uptake, with tumor/blood ratios up to 11.8:1 at 24 h. A radioiodinated preparation of SIP(G11) was also investigated in a double tracer study using an orthotopic rat glioma model, confirming the antibody's ability to preferentially localize at the tumor site, with tumor/brain ratios superior to the ones observed with (18)F-fluorodeoxyglucose. These tumor-targeting properties, together with the strong immunohistochemical staining of human tumor sections, indicate that the G11 antibody may be used as a portable targeting moiety for the selective delivery of imaging and therapeutic agents to gliomas and lung tumors.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TNCHumanglioblastoma  IEP  RGD 
TncRatglioblastoma  ISOTNC (Homo sapiens) RGD 
TncMouseglioblastoma  ISOTNC (Homo sapiens) RGD 
TNCHumanhigh grade glioma  ISOTnc (Rattus norvegicus)protein:increased expression:brainRGD 
TncRathigh grade glioma  IEP protein:increased expression:brainRGD 
TncMousehigh grade glioma  ISOTnc (Rattus norvegicus)protein:increased expression:brainRGD 
TNCHumanlung cancer  IEP protein:increased expression:lungRGD 
TncRatlung cancer  ISOTNC (Homo sapiens)protein:increased expression:lungRGD 
TncMouselung cancer  ISOTNC (Homo sapiens)protein:increased expression:lungRGD 
TNCHumanMesothelioma  IEP  RGD 
TncRatMesothelioma  ISOTNC (Homo sapiens) RGD 
TncMouseMesothelioma  ISOTNC (Homo sapiens) RGD 
TNCHumanNeoplasm Metastasis  IEP associated with Carcinoma more ...RGD 
TncRatNeoplasm Metastasis  ISOTNC (Homo sapiens)associated with Carcinoma more ...RGD 
TncMouseNeoplasm Metastasis  ISOTNC (Homo sapiens)associated with Carcinoma more ...RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TncRatbud outgrowth involved in lung branching  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tnc  (tenascin C)

Genes (Mus musculus)
Tnc  (tenascin C)

Genes (Homo sapiens)
TNC  (tenascin C)


Additional Information