Neoadjuvant anti-tumor vaccination prior to surgery enhances survival

Journal of Translational Medicine

Richard A Lake²  Bruce WS Robinson²  W Joost Lesterhuis²  Ben Wylie¹  Theresa Connor¹  Andrea Khong²  Devina D Lakhiani²  Amanda Cleaver²  Scott A Fisher² 

[1]School of Medicine & Pharmacology, University of Western Australia, Perth, 4th Floor, G Block, Queen Elizabeth II Medical Centre, Perth 6009, WA, Australia

[2]National Research Centre for Asbestos Related Diseases, Harry Perkins Institute of Medical Research, QQ Block, 6 Verdun Street, Nedlands 6009, WA, Australia

关键词: Neoadjuvant;    Cancer immunotherapy;    Lymphocytes;    Cancer vaccine;    Surgery;   

Others  :  1148222
DOI  :  10.1186/s12967-014-0245-7

 received in 2014-03-13, accepted in 2014-08-26,  发布年份 2014

【 摘 要 】

Background

This study was conducted to determine if anti-tumor vaccination administered prior to partial debulking surgery could improve survival using a murine solid tumour model.

Methods

Tumor incidence and survival rates were compared in mice bearing subcutaneous AB1-HA mesothelioma tumors that received either sham surgery, debulking surgery or vaccination prior to debulking surgery. Additionally, mice were depleted of CD4 and/or CD8 T lymphocytes during vaccination to assess their involvement in vaccine induced anti-tumor immunity. Flow cytometry was performed to characterise changes in the proportion and activation status of immune cells associated with anti-tumor immunity.

Results

Neoadjuvant vaccination combined with debulking surgery resulted in decreased tumor burden, increased survival and generation of tumor-specific immunity compared to surgery alone. Depletion of CD8 T cells completely abrogated any vaccine induced anti-tumor immune response. Conversely, CD4 depletion enhanced CD8 T cell activation resulting in complete tumor regression in 70% of mice treated with combined surgery and vaccination therapy. Tumor free survival was associated with established immunological memory as defined by the induction of effector memory T cells and resistance to rechallenge with parental AB1 mesothelioma cells.

Conclusions

Neoadjuvant anti-cancer vaccination combined with partial debulking surgery induced CD8-dependent anti-tumor immunity that significantly delayed tumor outgrowth relative to surgery alone. Complete tumor eradication was observed when vaccination and surgery were performed in CD4 T cell depleted animals. This demonstrates that adjuvant immunotherapy can improve post-surgical survival following cancer debulking surgery and provides a scientific rational for clinical trials of such an approach.

【 授权许可】

   
2014 Fisher et al.; licensee BioMed Central Ltd.

【 图 表 】

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