Mycobacterial Ag85A-Ag85B double gene adenovirus inhibits lewis lung cancer growth in mice

Background: Immunotherapy is the most promising novel treatment for cancer and expected to achieve breakthrough in near future because of improvement in the understanding of the tumor immunology. The present study is aimed to pave way to explore possibility and approaches of active immunotherapy for lung cancer based on DNA vaccines containing antigen genes of mycobacterial Ag85A and Ag85B. Methods: Mycobacterial antigen genes adenovirus Ad-Ag85A-Ag85B-CMV was constructed. Lewis lung cancer (LLC) cells were infected with Ad-Ag85AAg85B-CMV and then Ag85A and Ag85 expression was detected with Western blot. Splenocytes of C57BL/6 mice that were vaccinated with Bacillus Calmette-Guerin (BCG) 6 weeks before were separated and co-cultured with AdAg85A-Ag85B-CMV infected LLC cells. Interleukin-2 (IL-2) and interferon-γ (IFN-γ) in co-culture medium was detected by enzyme-linked immunosorbent assay (ELISA). LLC bearing mice were developed with C57BL/6 mice vaccinated with BCG 6 weeks before. Then, Ad-Ag85A-Ag85B-CMV was intra-tumorally injected so that its inhibitory effect for LLC in mice could be observed. Results: Mycobacterial antigens of Ag85A and Ag85B were detected in Ad-Ag85AAg85B-CMV transfected LLC cells with Western blot. An elevation of IL-2 and IFN-γ in co-culture medium was detected by ELISA, compared with empty adenovius and blank control. Average weight of tumors in mice of BCG vaccination and Ad-Ag85A-Ag85B-CMV treatment group was significantly lower than control groups. Conclusion: Immune gene-therapy using mycobacterial antigen genes of Ag85A and Ag85B is promising novel treatment for lung cancer.

[1]  R. Herbst,et al.  Immunotherapy in Lung Cancer. , 2017, Hematology/oncology clinics of North America.

[2]  R. Walker,et al.  A double-blind, randomised, placebo-controlled, dose-finding trial of the novel tuberculosis vaccine AERAS-402, an adenovirus-vectored fusion protein, in healthy, BCG-vaccinated infants. , 2015, Vaccine.

[3]  T. Jiang,et al.  The past, present and future of immunotherapy against tumor. , 2015, Translational lung cancer research.

[4]  R. Mancini,et al.  Xenogene vaccination in the therapy of cancer , 2014, Expert opinion on biological therapy.

[5]  R. Schreiber,et al.  New insights into cancer immunoediting and its three component phases--elimination, equilibrium and escape. , 2014, Current opinion in immunology.

[6]  A. Whelan,et al.  Comparison of the immunogenicity and protection against bovine tuberculosis following immunization by BCG-priming and boosting with adenovirus or protein based vaccines. , 2014, Vaccine.

[7]  Ioanna Kougioumtzi,et al.  Lung cancer surgery: an up to date. , 2013, Journal of thoracic disease.

[8]  D. Pei,et al.  A novel DNA vaccine expressing the Ag85A-HA2 fusion protein provides protection against influenza A virus and Staphylococcus aureus , 2013, Virology Journal.

[9]  W. Leonard,et al.  Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy. , 2013, Immunity.

[10]  E. Wang,et al.  Dendritic cell vaccine modified by Ag85A gene enhances anti-tumor immunity against bladder cancer. , 2012, International immunopharmacology.

[11]  Drew M. Pardoll,et al.  The blockade of immune checkpoints in cancer immunotherapy , 2012, Nature Reviews Cancer.

[12]  Gemma K. Alderton,et al.  Tumour immunotherapy — leukocytes take up the fight , 2012, Nature Reviews Immunology.

[13]  William Pao,et al.  Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer , 2010, Nature Reviews Cancer.

[14]  L. Marks,et al.  Local recurrence after surgery for early stage lung cancer , 2009, Cancer.

[15]  H. McShane,et al.  Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans , 2004, Nature Medicine.

[16]  Dah-Shyong Yu,et al.  Immunotherapy for bladder cancer using recombinant bacillus Calmette-Guerin DNA vaccines and interleukin-12 DNA vaccine. , 2004, The Journal of urology.

[17]  M. Shimizu,et al.  A novel method for modification of tumor cells with bacterial superantigen with a heterobifunctional cross-linking agent in immunotherapy of cancer , 2003, Molecular biotechnology.

[18]  G. Besra,et al.  Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis. , 1997, Science.

[19]  C. Gatsonis,et al.  Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening , 2012 .

[20]  J. Bubeník.  MHC class I down regulation, tumour escape from immune surveillance and design of therapeutic strategies. , 2005, Folia biologica.