Targeting pancreatic and ovarian carcinomas using the auristatin-based anti-CD70 antibody-drug conjugate SGN-75.
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.


CONCLUSIONS
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.
Ryan
M C
MC
Seattle Genetics, Inc. 21823 - 30th Drive SE, Bothell, WA 98021, USA.
Kostner
H
H
Gordon
K A
KA
Duniho
S
S
Sutherland
M K
MK
Yu
C
C
Kim
K M
KM
Nesterova
A
A
Anderson
M
M
McEarchern
J A
JA
Law
C-L
CL
Smith
L M
LM
D062365:Aminobenzoates / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D053282:CD27 Ligand / Q000276:immunology*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000008:administration & dosage*; D010051:Ovarian Neoplasms / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000628:therapy*
D062365:Aminobenzoates; D000911:Antibodies, Monoclonal; D053282:CD27 Ligand; D018796:Immunoconjugates; D009842:Oligopeptides; C543533:auristatin