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Open Access Research

Enhanced antitumoral efficacy and immune response following conditionally replicative adenovirus containing constitutive HSF1 delivery to rodent tumors

Rong Fan1, Cheng Wang2, Yang Wang1, Ping Ren1, Pingping Gan3, Hui Ji1, Zian Xia1, Suiyu Hu1, Qiongyao Zeng1, Wei Huang1, Yebin Jiang4 and Xi Huang1*

Author Affiliations

1 Department of Integrative Medicine of Traditional Chinese Medicine and Western Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China

2 Institute of Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

3 Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China

4 Osteoporosis and Arthritis Lab, Department of Radiology, University of Michigan, Ann Arbor, MI, 48109, USA

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Journal of Translational Medicine 2012, 10:101  doi:10.1186/1479-5876-10-101

Published: 21 May 2012

Abstract

Background

Oncolytic adenoviruses are promising as anticancer agents but have limited clinical responses. Our previous study showed that heat shock transcription factor 1 (HSF1) overexpression could increase the anti-tumor efficacy of E1B55kD deleted oncolytic adenovirus through increasing the viral burst. Due to the important roles of heat shock proteins (HSPs) in eliciting innate and adaptive immunity, we reasoned that besides increasing the viral burst, HSF1 may also play a role in increasing tumor specific immune response.

Methods

In the present study, intra-dermal murine models of melanoma (B16) and colorectal carcinoma (CT26) were treated with E1B55kD deleted oncolytic adenovirus Adel55 or Adel55 incorporated with cHSF1, HSF1i, HSP70, or HSP90 by intra-tumoral injection. Tumors were surgically excised 72 h post injection and animals were analyzed for tumor resistance and survival rate.

Results

Approximately 95% of animals in the Adel55-cHSF1 treated group showed sustained resistance upon re-challenge with autologous tumor cells, but not in PBS, Adel55, or Adel55-HSF1i treated groups. Only 50–65% animals in the Adel55-HSP70 and Adel55-HSP90 treated group showed tumor resistance. Tumor resistance was associated with development of tumor type specific cellular immune responses. Adel55-cHSF1 treatment also showed higher efficacy in diminishing progression of the secondary tumor focus than Adel55-HSP70 or Adel55-HSP90 treatment.

Conclusions

Besides by increasing its burst in tumor cells, cHSF1 could also augment the potential of E1B55kD deleted oncolytic adenovirus by increasing the tumor-specific immune response, which is beneficial to prevent tumor recurrence. cHSF1 is a better gene for neoadjuvant immunotherapy than other heat shock protein genes.

Keywords:
HSF1; Cancer immunotherapy; Oncolytic adenovirus