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Published on: June 13, 2014
Targeting pancreatic and ovarian carcinomas using the auristatin-based anti-CD70 antibody-drug conjugate SGN-75
M C Ryan1, H Kostner, K A Gordon
1Seattle Genetics, Inc. 21823 - 30th Drive SE, Bothell, WA 98021, USA.
Background:
CD70 is an ideal target for antibody-based therapies because of its aberrant high expression in renal carcinomas and non-Hodgkin lymphomas and its highly restricted expression in normal tissues. The expression profiling of CD70 in carcinomas has been limited because of the lack of a CD70-specific reagent that works in formalin-fixed paraffin-embedded (FFPE) tissues.
Methods:
We generated murine monoclonal antibodies (mAbs) specific for CD70 and validated their specificity by western blot analysis and developed a protocol for immunohistochemistry on FFPE tissues. CD70+ tumour cell lines were used for testing the anti-tumour activity of the anti-CD70 antibody-drug conjugate, SGN-75.
Results:
We report novel detection of CD70 expression in multiple cancers including pancreatic (25%), larynx/pharynx (22%), melanoma (16%), ovarian (15%), lung (10%), and colon (9%). Our results show that pancreatic and ovarian tumour cell lines, which express high levels of endogenous or transfected CD70, are sensitive to the anti-tumour activity of SGN-75 in vitro and in vivo.
Conclusion:
Development of murine mAbs for robust and extensive screening of FFPE samples coupled with the detection of anti-tumour activity in novel indications provide rationale for expanding the application of SGN-75 for the treatment of multiple CD70 expressing cancers.
Insights
New monoclonal antibodies (mAbs) enable detection of CD70 in various cancers. This supports the use of SGN-75 antibody-drug conjugate for treating multiple CD70-expressing tumors.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- CD70 is a promising target for antibody therapies due to its high expression in renal carcinomas and non-Hodgkin lymphomas.
- Limited CD70 expression profiling in carcinomas is due to the lack of specific reagents for formalin-fixed paraffin-embedded (FFPE) tissues.
Purpose of the Study:
- To develop novel murine monoclonal antibodies (mAbs) specific for CD70.
- To establish an immunohistochemistry protocol for FFPE tissues.
- To evaluate the anti-tumor activity of the CD70-targeted antibody-drug conjugate, SGN-75.
Main Methods:
- Generation and validation of CD70-specific murine mAbs using western blot analysis.
- Development of an immunohistochemistry protocol for FFPE tissue samples.
- In vitro and in vivo testing of SGN-75 anti-tumor activity on CD70+ tumor cell lines.
Main Results:
- Novel detection of CD70 expression in pancreatic (25%), larynx/pharynx (22%), melanoma (16%), ovarian (15%), lung (10%), and colon (9%) cancers.
- Pancreatic and ovarian tumor cell lines with high CD70 expression showed sensitivity to SGN-75.
- Demonstrated in vitro and in vivo anti-tumor activity of SGN-75.
Conclusions:
- Murine mAbs enable robust screening of CD70 expression in FFPE samples across multiple cancers.
- The anti-tumor activity of SGN-75 in novel indications warrants further investigation.
- Expanded application of SGN-75 for treating various CD70-expressing cancers is supported.
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