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Combining Prime-Boost Anti-tumour Vaccination with Debulking Surgery for the Treatment of Solid Tumours

Scott FISHER1*, Amanda Cleaver1, Andrea Khong1, Ben Wylie1, Daphne Lakhiani1, Catherine Boylen1, Theresa Connor1, Bruce Robinson1 and Richard Lake1
  • 1 The University of Wesern Australia, School of Medicine and Pharmacology, Australia

The development of effective anti-cancer immunotherapies is of critical importance. While many anti-cancer immunotherapies have had limited success as monotherapies, their efficacy may be enhanced when combined with conventional therapies such as surgery or chemotherapy. Here we describe the development of a prime-boost (P/B) anti-tumour vaccination protocol that significantly improved survival outcome when combined with partial debulking surgery and targeted suppression of regulatory T cells (Treg).


Using our well established AB1-HA mouse tumour model, tumour bearing mice received prime (influenza A PR/8/34/H1N1; PR8) and boost (HA expressing recombinant modified Vaccinia Ankara; rMVA HA) vaccinations either before (neoadjuvant) or after (adjuvant) 75% debulking surgery. Only neoadjuvant P/B vaccination induced tumour specific immunity that resulted in significantly delayed tumour growth when combined with debulking surgery; although this was not sufficient to prevent tumour outgrowth. Depletion studies demonstrated that CD8 T cells were essential for the delay in tumour growth. Interestingly, depletion of CD4 T cells and more specifically Treg during neoadjuvant P/B vaccination lead to cures in greater than 60% of treated mice. These surviving mice also resisted tumour rechallenged indicating the establishment of long term anti-tumour immunological memory.


Taken together, these data suggest that vaccine induced anti-tumuor immunity is “restrained” by Treg and can be enhanced by the targeted removal of Treg. Based on these findings we are actively investigating whether combining novel immunotherapies with conventional treatments in the absence of “immunological restrainers” such as Treg and myeloid derived suppressor cells (MDSC) may generate effective therapy for MM and other solid cancers.

Acknowledgements

Support: This research was funded by a research grant from the Workers’ Compensation Dust Diseases Board, an agency of the New South Wales Government.

Keywords: Cancer, Immunotherapy, regulatory T cells, anti-tumour vaccines, Surgery., combination therapy, mouse model

Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.

Presentation Type: Abstract

Topic: Translational immunology and immune intervention

Citation: FISHER S, Cleaver A, Khong A, Wylie B, Lakhiani D, Boylen C, Connor T, Robinson B and Lake R (2013). Combining Prime-Boost Anti-tumour Vaccination with Debulking Surgery for the Treatment of Solid Tumours. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00650

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Received: 13 Jun 2013; Published Online: 22 Aug 2013.

* Correspondence: Dr. Scott FISHER, The University of Wesern Australia, School of Medicine and Pharmacology, Perth, Western Australia, 6009, Australia, scott.fisher@uwa.edu.au