Regression of devil facial tumour disease following immunotherapy in immunised Tasmanian devils

Cesar Tovar,Yuanyuan Cheng,Katherine Belov,Anthony T Papenfuss,James M Murphy,Karsten Skjødt,Roslyn C Malley,Lynn M Corcoran,Jocelyn Darby,Anabel Silva,A Bruce Lyons,Alexandre Kreiss,Hannah V T Siddle,Jim Kaufman,Martin J Pearse,Ruth J Pye,Gabriella K Brown,Adriana Baz Morelli,Gregory M Woods

doi:10.1038/srep43827

Abstract

Devil facial tumour disease (DFTD) is a transmissible cancer devastating the Tasmanian devil (Sarcophilus harrisii) population. The cancer cell is the ‘infectious’ agent transmitted as an allograft by biting. Animals usually die within a few months with no evidence of antibody or immune cell responses against the DFTD allograft. This lack of anti-tumour immunity is attributed to an absence of cell surface major histocompatibility complex (MHC)-I molecule expression. While the endangerment of the devil population precludes experimentation on large experimental groups, those examined in our study indicated that immunisation and immunotherapy with DFTD cells expressing surface MHC-I corresponded with effective anti-tumour responses. Tumour engraftment did not occur in one of the five immunised Tasmanian devils, and regression followed therapy of experimentally induced DFTD tumours in three Tasmanian devils. Regression correlated with immune cell infiltration and antibody responses against DFTD cells. These data support the concept that immunisation of devils with DFTD cancer cells can successfully induce humoral responses against DFTD and trigger immune-mediated regression of established tumours. Our findings support the feasibility of a protective DFTD vaccine and ultimately the preservation of the species.

Highlights

The challenge. (c) TD4-Mm (Protocol C) did not develop tumours after the challenge with live Devil facial tumour disease (DFTD) cells. (d) Development of grafted DFTD tumours in devils immunised with Protocol D
Seven devils were immunised with a variety of cell preparations and adjuvants to determine if they could be protected against the development of DFTD following challenge with live DFTD cells
As devils were immunised with either major histocompatibility complex class I (MHC-I)+ or MHC-I− DFTD cells, antibody reactivity was evaluated against cytokine treated (MHC-I+) and untreated (MHC-I−) DFTD cells

Summary

Introduction

The challenge. (c) TD4-Mm (Protocol C) did not develop tumours after the challenge with live DFTD cells. (d) Development of grafted DFTD tumours in devils immunised with Protocol D. The images are representative histology of a biopsy from the LHS tumour taken 14 weeks after challenge showing very poor immune cell infiltration. The images show no evidence of immune cell infiltration in a biopsy of the LHS tumour taken 20 weeks after challenge. A biopsy of the LHS tumour taken 10 weeks after challenge shows scattered MHC-II+ cells within the tumour and very occasional CD3+ cells. In this study we sought to establish whether induction of MHC-I expression on DFTD cells as components of immunisations and immunotherapy would correspond with anti-DFTD tumour responses. TM of ISCOMATRIX , Poly I:C and CpG These adjuvants promote innate, humoral and cell mediated anti-tumour immunity[11,12,13]. This paper illustrates the potential for vaccination to induce humoral responses and, with additional immunotherapy, trigger DFTD immune-mediated regression in vivo

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Conclusion