Neuropilin-1 drives tumor-specific uptake of chlorotoxin

Table 2 Correlation of ER-472 antitumor activity to NRP1 expression in tumor lysates in multiple xenograft models. Antitumor activity was assessed for ER-472 administered i.v. on a Q4Dx3 schedule, at ¼ to full MTD doses in multiple xenograft models. NRP1 expression in tumors was assessed by mRNA analysis and/or protein detection by western blot or IHC. Reasonable correlation was determined for 11 of the 13 models

Xenograft Model	Antitumor Activity			Human NRP1 Expression	Correlation of efficacy to NRP1
Xenograft Model	MTD	½ MTD	¼ MTD	Human NRP1 Expression	Correlation of efficacy to NRP1
MIA PaCa-2	++++	–	nd	low	yes
BxPC3	++	–	nd	low	yes
PC-3	++++	++++	++	high	yes
SK-N-MC	–	nd	nd	low	yes
TC-71	–	nd	nd	low	yes
MDA-MB-231	++++	+	+	high	yes
HT-1080	+++	++	–	high	yes
U-87 MG	+++	++	+/−	high	yes
COLO 320DM	+/−	–	nd	low	yes
Hs 695 T	++++	+++	+	low^a	no
CFPAC-1	+	–	–	low^b	yes^b
LOX IMVI	++	–	–	high	no
HCT 116	nd	–	nd	low	yes

^aNRP1 expressed at high level in cell line was lost in tumors
^bhigh NRP1 expression in tumor lysate by western subsequently deemed predominantly stromal by IHC; CFPAC-1 tumor cells had low NRP1 staining, a likely explanation for poor ER-472 therapeutic activity

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