Cancer Immunology, Immunotherapy

, Volume 56, Issue 10, pp 1605–1613

Eradication of hepatoma and colon cancer in mice with Flt3L gene therapy in combination with 5-FU

  • Sheng Hou
  • Geng Kou
  • Xiaoqiang Fan
  • Hao Wang
  • Weizhu Qian
  • Dapeng Zhang
  • Bohua Li
  • Jianxin Dai
  • Jian Zhao
  • Jing Ma
  • Jing Li
  • Birong Lin
  • Mengchao Wu
  • Yajun Guo
Original Article

DOI: 10.1007/s00262-007-0306-3

Cite this article as:
Hou, S., Kou, G., Fan, X. et al. Cancer Immunol Immunother (2007) 56: 1605. doi:10.1007/s00262-007-0306-3

Abstract

We developed a recombinant defective adenovirus with an insert of gene encoding extracellular domain of mouse Flt3L (Ad-mFlt3L) under control of cytomegalovirus promoter to investigate the biological efficacy of Flt3L in combination with chemotherapeutical drug, 5-FU, in eliciting an effective anti-cancer immunity in mouse hepatoma and colon cancer model systems. The constructed Ad-mFlt3L efficiently infected hepatoma and colon cancer cells both in vitro and in vivo, leading to a high production of mFlt3L proteins in association with accumulation of DCs, NK cells and lymphocytes in local tumor tissues. Administration of Ad-mFlt3L can protect bone marrow injury caused by 5-Fu and stimulates proliferation and maturation of lymphocytes, APCs and NKs. Intratumoral injection of Ad-mFlt3L followed by an intraperitoneal administration of 5-Fu significantly inhibited tumor growth and cured established tumors. Adenovirus mediated Flt3L gene therapy synergies with chemotherapeutic drug, 5-Fu, in elicitation of long-lasting antitumor immunity. The tumor specific immunity can be adoptively transferred into naïve animals successfully by transfusion of CD3+CD8+ T cells from the treated mice. The data suggests that adenovirus mediated Flt3L gene therapy in combination with 5-Fu chemotherapy may open a new avenue for development of anti-cancer chemogenetherapy.

Keywords

HepatomaColon cancer5-FuFlt3LImmunity

Abbreviations

Flt3L

Fms-like tyrosine kinase 3 ligand

NK

Natural killer

HCC

Hepatocellular carcinoma

5-Fu

5-Fluorouracil

MEM

Minimal essential medium

Ad-mFL

Adenovirus with an insert of gene encoding extracellular domain of mouse Flt3L

MTT

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

FBS

Fetal bovine serum

CMV

Cytomegalovirus

EFU

Expression-forming unit

CFU

Colony-forming unit

BFU

Burst-forming unit

MOI

Multiplicity of infection

IHC

Immunohistochemistry

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Sheng Hou
    • 1
    • 2
  • Geng Kou
    • 1
    • 2
  • Xiaoqiang Fan
    • 1
  • Hao Wang
    • 1
    • 2
  • Weizhu Qian
    • 1
    • 2
  • Dapeng Zhang
    • 1
  • Bohua Li
    • 1
    • 2
  • Jianxin Dai
    • 1
  • Jian Zhao
    • 1
  • Jing Ma
    • 1
  • Jing Li
    • 1
    • 2
  • Birong Lin
    • 2
  • Mengchao Wu
    • 1
  • Yajun Guo
    • 1
    • 2
  1. 1.International Joint Cancer Institute and Institute of Hepatobiliary SurgeryThe Second Military Medical UniversityShanghaiPeople’s Republic of China
  2. 2.Shanghai Center for Cell Engineering and Antibody, Research BuildingShanghaiPeople’s Republic of China