Photodynamic therapy with recombinant adenovirus AdmIL-12 enhances anti-tumour therapy efficacy in human papillomavirus 16 (E6/E7) infected tumour model

Immunology. 2008 Aug;124(4):461-8. doi: 10.1111/j.1365-2567.2007.02797.x. Epub 2008 Apr 4.


Immunotherapy with photodynamic therapy (PDT) offers great promise as a new alternative for cancer treatment; however, its use remains experimental. Here we investigated the utility of adenoviral delivery of interleukin-12 (AdmIL-12) as an adjuvant for PDT in mouse tumour challenge model. PDT was performed by irradiating Radachlorin in C57BL/6 mice transplanted with TC-1 cells. PDT plus AdmIL-12 treatment for tumour suppression as well as specific immune responses were evaluated with the following tests: in vitro and in vivo tumour growth inhibition, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) assay, and cytotoxic T lymphocyte (CTL) assay. Direct intratumoral injection of AdmIL-12 resulted in a significant suppression of tumour growth compared to the control group. Treatment of PDT along with AdmIL-12 further enhanced antitumour effects significantly higher than either AdmIL-12 or PDT alone. This combined treatment resulted in complete regression of 9-mm sized tumour in every animal. We also evaluated immune responses induced by these treatments. Combined treatment significantly increased the production level of IFN-gamma and TNF-alpha compared with that by AdmIL-12 or PDT alone. PDT plus AdmIL-12 enhanced antitumour immunity through increased expansion of the CTL subset mediated by CD8+ T cells. Taken together, these results indicate that the high anti-cancer activity of PDT with AdmIL-12 is a powerful tool against cancer therapy and is a promising subject for further investigation.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Combined Modality Therapy
  • Cytotoxicity, Immunologic
  • Female
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Human papillomavirus 16*
  • Immunity, Cellular
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / genetics*
  • Interleukin-12 / immunology
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / therapy*
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / therapy*
  • Photochemotherapy / methods*
  • Photosensitizing Agents / pharmacokinetics
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Photosensitizing Agents
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Interferon-gamma