Gene therapy with secretory leukoprotease inhibitor promoter-controlled replication-competent adenovirus for non-small cell lung cancer

Cancer Research
Makoto MaemondoToshihiro Nukiwa

Abstract

Secretory leukoprotease inhibitor (SLPI) is highly expressed in almost all non-small cell lung cancers (NSCLCs), but not in the majority of other tumor types. In an attempt to create a specific gene therapy for NSCLC, we constructed AdSLPI.E1AdB, an adenovirus vector with a double expression cassette consisting of E1A driven by the SLPI promoter gene followed by E1B-19K under the control of the cytomegalovirus (CMV) promoter that can selectively replicate only in NSCLC cells. Infection with AdSLPI.E1AdB yielded E1A protein expression and adenovirus replication resulting in a >100-fold increase of the virus titers only in SLPI-producing NSCLC cells (A549, H358, and HS24 cells). In contrast, neither E1A protein nor replication was detected in non-SLPI-producing HepG2 cells. Treatment with AdSLPI.E1AdB significantly inhibited the proliferation of NSCLC cells in vitro in a dose-dependent manner, whereas the cell growth of HepG2 or normal human bronchial epithelial cells was not affected by AdSLPI.E1AdB infection. Direct injection of AdSLPI.E1AdB into A549 and H358 tumors in nude mice resulted in a marked reduction in tumor growth compared with controls (A549, 57%, P < 0.02; H358, 67%, P < 0.03). Histological examination revealed th...Continue Reading

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Citations

Jun 14, 2005·Biochemical and Biophysical Research Communications·Kunio Matsumoto, Toshikazu Nakamura
Jul 11, 2006·Biochemistry. Biokhimii︠a︡·E M GlinkaS M Deyev
Nov 28, 2013·Carcinogenesis·Cezary Jan TredaToshihiro Nukiwa
Apr 28, 2009·Advanced Drug Delivery Reviews·Dominik E Dorer, Dirk M Nettelbeck
Apr 3, 2008·Cancer Science·Toshihiro NukiwaToshiaki Kikuchi
Jul 23, 2008·Proteomics·Kunio MatsumotoToshikazu Nakamura
Jul 21, 2005·Technology in Cancer Research & Treatment·Masato Yamamoto, David T Curiel
Feb 4, 2006·The Lancet Oncology·Dominique BouchardGuy M Tremblay
Feb 8, 2005·Clinical Lung Cancer·Thomas T PoulsenHans S Poulsen

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