Photodynamic therapy with recombinant adenovirus AdmIL-12 enhances anti-tumour therapy efficacy in human papillomavirus 16 (E6/E7) infected tumour model.
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.
Park
Eun Kyung
EK
Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Bae
Su-Mi
SM
Kwak
Sun-Young
SY
Lee
Sung Jong
SJ
Kim
Yong-Wook
YW
Han
Chan-Hee
CH
Cho
Hyun-Jung
HJ
Kim
Kyung Tae
KT
Kim
Young-Jae
YJ
Kim
Hyun-Jung
HJ
Ahn
Woong Shick
WS
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D052162:Human papillomavirus 16; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D030361:Papillomavirus Infections / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D017319:Photosensitizing Agents; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma