US 9,808,505 B2
Suppression of malignant mesothelioma by overexpression or stimulation of endothelial protein C receptors (EPCR)
Usha R. Pendurthi, Tyler, TX (US); Vijaya M. R. Lella, Tyler, TX (US); Shivakeshava Gaddam, Tyler, TX (US); and Steven Idell, Tyler, TX (US)
Assigned to BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM, Austin, TX (US)
Appl. No. 14/765,922
Filed by BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM, Austin, TX (US)
PCT Filed Mar. 10, 2014, PCT No. PCT/US2014/022373
§ 371(c)(1), (2) Date Aug. 5, 2015,
PCT Pub. No. WO2014/138727, PCT Pub. Date Sep. 12, 2014.
Claims priority of provisional application 61/775,251, filed on Mar. 8, 2013.
Prior Publication US 2015/0366939 A1, Dec. 24, 2015
Int. Cl. A61K 38/17 (2006.01); A61K 48/00 (2006.01); C12N 15/113 (2010.01); A61K 9/00 (2006.01); A61K 31/4439 (2006.01); A61K 31/5377 (2006.01); A61K 38/19 (2006.01); A61K 38/21 (2006.01)
CPC A61K 38/177 (2013.01) [A61K 9/007 (2013.01); A61K 9/0019 (2013.01); A61K 31/4439 (2013.01); A61K 31/5377 (2013.01); A61K 38/191 (2013.01); A61K 38/217 (2013.01); A61K 48/005 (2013.01); A61K 48/0058 (2013.01); C12N 15/113 (2013.01); C12N 2310/14 (2013.01); C12N 2310/531 (2013.01); C12N 2710/10343 (2013.01); C12N 2710/10371 (2013.01)] 3 Claims
 
1. A method of sensitizing malignant pleural mesothelioma (MPM) cells to killing by endogenous cytokines in a subject in need thereof, said method comprising transducing MPM cells to express Endothelial Protein C Receptor (EPCR), by exposing them to a nucleic acid expression vector, wherein said vector is administered intrapleurally to said subject, the vector comprising a nucleotide sequence comprising:
(i) an EPCR-coding sequence consisting of the nucleotide of SEQ ID NO:1 encoding the EPCR of SEQ ID NO:2, said nucleic acid EPCR-coding sequence operably linked to a promoter to express said EPCR-coding sequence in MPM cells, and said nucleic acid EPCR-coding sequence optionally linked to
(ii) an enhancer and/or other expression control element for expression of EPCR in the MPM cells,
wherein cells so transduced and expressing EPCR are sensitized to killing by endogenous cytokines interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα) compared to MPM cells not so transduced that are not so sensitized to such killing.