US 11,744,877 B2
Method for permeabilizing tumor vasculature using a tumor vasculature permeabilizing molecule to improve access of a therapeutic or diagnostic agent to a tumor
Daniel Anthony, Oxford (GB); Nicola Sibson, Oxford (GB); Len Seymour, Oxford (GB); and Kerry Fisher, Oxford (GB)
Assigned to OXFORD UNIVERSITY INNOVATION LIMITED, Oxford (GB)
Appl. No. 13/514,138
Filed by Daniel Anthony, Oxford (GB); Nicola Sibson, Oxford (GB); Len Seymour, Oxford (GB); and Kerry Fisher, Oxford (GB)
PCT Filed Dec. 8, 2010, PCT No. PCT/GB2010/052048
§ 371(c)(1), (2), (4) Date Nov. 19, 2012,
PCT Pub. No. WO2011/070358, PCT Pub. Date Jun. 16, 2011.
Claims priority of application No. 0921525 (GB), filed on Dec. 8, 2010.
Prior Publication US 2013/0101550 A1, Apr. 25, 2013
Int. Cl. A61K 38/19 (2006.01); A61K 45/06 (2006.01); A61K 49/00 (2006.01)
CPC A61K 38/191 (2013.01) [A61K 45/06 (2013.01); A61K 49/0002 (2013.01)] 28 Claims
 
1. A method of detecting a metastatic brain tumor behind an intact blood brain barrier in a patient who has a peripheral primary tumor, said method comprising
systemically administering to the patient a signal generating agent and a proinflammatory cytokine, wherein the proinflammatory cytokine binds specifically to TNF-receptor TNFR-1 or TNFR-2, and wherein the proinflammatory cytokine is administered at a sub-therapeutic dose for the treatment of tumors, wherein the sub-therapeutic dose of the proinflammatory cytokine is not cytotoxic to a brain tumor and/or does not cause tumor regression when administered systemically, wherein the sub-therapeutic dose of the proinflammatory cytokine permeabilizes pre-existing host vasculature adjacent to the metastatic brain tumor and disrupts the intact blood brain barrier of the metastatic brain tumor to improve access of the signal generating agent to the metastatic brain tumor, and
imaging the brain of the patient to detect the tumor, wherein the metastatic brain tumor is not detectable by imaging in the absence of the pro-inflammatory cytokine.