Table 1.

Description and characterization of a novel panel of uPA and uPAR targeted monoclonal antibodies with therapeutic potential. A panel of uPA and uPAR targeted antibodies with different epitope specificities has been developed. The biological and targeting activity of this panel is presently being evaluated in our laboratory. We hypothesize that the different epitope specificities and targeting either uPA or uPAR will allow us to dissect some of the basic biology of this system as well as identify antibodies that may not affect the biology of uPA/uPAR but may have utility as targeting agents. For example, ATN-292 inhibits the binding of uPA to uPAR by binding to the GFD of uPA but is not internalized. ATN-291 binds to the kringle domain of uPA, can bind to uPA when it is bound to uPAR and is internalized. Various targeting studies using ATN-291 are ongoing. ATN-616 and ATN-617 block the binding of uPA to uPAR but have little antitumor activity as monotherapies. ATN-615 and ATN-658 do not block the binding of uPA to uPAR and can bind to uPAR even when uPA is bound. Both of these antibodies are also internalized. The epitope for ATN-615 has been described ²³ and the antitumor activity of ATN-658 in multiple tumor models has also been published ³⁴, ⁷⁵-⁷⁷. ATN-615 and ATN-658 are also being evaluated as targeting agents in our laboratory.

Clone #	Antibody#	Specificity	Isotype	Kd, nM (ELISA)	Kd, nM (HeLa)
ATF-392	ATN-291	uPA (Kringle)	IgG1 κ	0.3	N.A.
ATF-1091	ATN-292	uPA (GFD)	IgG1 κ	0.5	N.A.
234E-33	ATN-615	D2D3	IgG1 κ	2	1.3
234E-151	ATN-658	D2D3	IgG1 κ	1	5.4
234E-174	ATN-616	D2D3	IgG1 κ	5	0.6
234E-180	ATN-617	D2D3	IgG1 κ	29	1.3