RGD Reference Report - Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma. - Rat Genome Database

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Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma.

Authors: Polson, Andrew G  Yu, Shang-Fan  Elkins, Kristi  Zheng, Bing  Clark, Suzanna  Ingle, Gladys S  Slaga, Dionysos S  Giere, Lynne  Du, Changchun  Tan, Christine  Hongo, Jo-Anne  Gogineni, Alvin  Cole, Mary J  Vandlen, Richard  Stephan, Jean-Philippe  Young, Judy  Chang, Wesley  Scales, Suzie J  Ross, Sarajane  Eaton, Dan  Ebens, Allen 
Citation: Polson AG, etal., Blood. 2007 Jul 15;110(2):616-23. doi: 10.1182/blood-2007-01-066704. Epub 2007 Mar 20.
RGD ID: 151665154
Pubmed: PMID:17374736   (View Abstract at PubMed)
DOI: DOI:10.1182/blood-2007-01-066704   (Journal Full-text)

Targeting cytotoxic drugs to cancer cells using antibody-drug conjugates (ADCs), particularly those with stable linkers between the drug and the antibody, could be an effective cancer treatment with low toxicity. However, for stable-linker ADCs to be effective, they must be internalized and degraded, limiting potential targets to surface antigens that are trafficked to lysosomes. CD79a and CD79b comprise the hetrodimeric signaling component of the B-cell receptor, and are attractive targets for the use of ADCs because they are B-cell-specific, expressed in non-Hodgkin lymphomas (NHL), and are trafficked to a lysosomal-like compartment as part of antigen presentation. We show here that the stable-linker ADCs anti-CD79b-MCC-DM1 and anti-CD79b-MC-MMAF are capable of target-dependent killing of nonHodgkin lymphoma cell lines in vitro. Further, these 2 ADCs are equally effective as low doses in xenograft models of follicular, mantle cell, and Burkitt lymphomas, even though several of these cell lines express relatively low levels of CD79b in vivo. In addition, we demonstrate that anti-CD79b ADCs were more effective than anti-CD79a ADCs and that, as hypothesized, anti-CD79b antibodies downregulated surface B-cell receptor and were trafficked to the lysosomal-like major histocompatibility complex class II-positive compartment MIIC. These results suggest that anti-CD79b-MCC-DM1 and anti-CD79b-MC-MMAF are promising therapeutics for the treatment of NHL.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CD79BHumanBurkitt lymphoma treatmentIMP human cells in mouse modelRGD 
Cd79bRatBurkitt lymphoma treatmentISOCD79B (Homo sapiens)human cells in mouse modelRGD 
Cd79bMouseBurkitt lymphoma treatmentISOCD79B (Homo sapiens)human cells in mouse modelRGD 
CD79BHumanfollicular lymphoma treatmentIMP human cells in mouse modelRGD 
Cd79bRatfollicular lymphoma treatmentISOCD79B (Homo sapiens)human cells in mouse modelRGD 
Cd79bMousefollicular lymphoma treatmentISOCD79B (Homo sapiens)human cells in mouse modelRGD 
CD79BHumanmantle cell lymphoma treatmentIMP human cells in mouse modelRGD 
Cd79bRatmantle cell lymphoma treatmentISOCD79B (Homo sapiens)human cells in mouse modelRGD 
Cd79bMousemantle cell lymphoma treatmentISOCD79B (Homo sapiens)human cells in mouse modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cd79b  (CD79b molecule)

Genes (Mus musculus)
Cd79b  (CD79B antigen)

Genes (Homo sapiens)
CD79B  (CD79b molecule)


Additional Information