Research

The effects of DNA formulation and administration route on cancer therapeutic efficacy with xenogenic EGFR DNA vaccine in a lung cancer animal model

Ming-Derg Lai^1,2,3 , Meng-Chi Yen² , Chiu-Mei Lin^4,5 , Cheng-Fen Tu¹ , Chun-Chin Wang⁶ , Pei-Shan Lin⁶ , Huei-Jiun Yang¹ and Chi-Chen Lin^6,7

¹  Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Taiwan

²  Institute of Basic Medicine, College of Medicine, National Cheng Kung University, Taiwan

³  Center for Gene Regulation and Signal Transduction Research, National Cheng Kung University, Tainan, Taiwan

⁴  School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

⁵  Department of Emergency Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, R.O.C

⁶  Institute of Medical Technology, College of Life Science, National Chung Hsing University, Taiwan

⁷  Department of Medical Research and Education, Taichung-Veterans General Hospital, Taichung, Taiwan

author email corresponding author email

Genetic Vaccines and Therapy 2009, 7:2doi:10.1186/1479-0556-7-2

Published:	30 January 2009

Abstract

Background

Tyrosine kinase inhibitor gefitinib is effective against lung cancer cells carrying mutant epidermal growth factor receptor (EGFR); however, it is not effective against lung cancer carrying normal EGFR. The breaking of immune tolerance against self epidermal growth factor receptor with active immunization may be a useful approach for the treatment of EGFR-positive lung tumors. Xenogeneic EGFR gene was demonstrated to induce antigen-specific immune response against EGFR-expressing tumor with intramuscular administration.

Methods

In order to enhance the therapeutic effect of xenogeneic EGFR DNA vaccine, the efficacy of altering routes of administration and formulation of plasmid DNA was evaluated on the mouse lung tumor (LL2) naturally overexpressing endogenous EGFR in C57B6 mice. Three different combination forms were studied, including (1) intramuscular administration of non-coating DNA vaccine, (2) gene gun administration of DNA vaccine coated on gold particles, and (3) gene gun administration of non-coating DNA vaccine. LL2-tumor bearing C57B6 mice were immunized four times at weekly intervals with EGFR DNA vaccine.

Results

The results indicated that gene gun administration of non-coating xenogenic EGFR DNA vaccine generated the strongest cytotoxicty T lymphocyte activity and best antitumor effects. CD8(+) T cells were essential for anti-tumor immunityas indicated by depletion of lymphocytes in vivo.

Conclusion

Thus, our data demonstrate that administration of non-coating xenogenic EGFR DNA vaccine by gene gun may be the preferred method for treating EGFR-positive lung tumor in the future.