Heat-Shocking of Murine Malignant Mesothelioma Cells Enhances Their Effectiveness as an Autologous Anti-Tumour Vaccine

Background: Malignant mesothelioma (MM) is a highly aggressive, incurable asbestos-induced cancer for which treatment options are limited. Surgical resection can reduce tumour burden, but patients ultimately succumb to disease due to reoccurrence of unresectable tumour, highlighting the need for new treatment modalities. In this study we describe the use of an easily translatable heat shock (HS) treated autologous tumour lysate vaccine and discus its potential application as an adjunct therapy for treating MM. Methods: Heat shocked autologous tumour lysate (HSL) vaccine was generated from AE17sOVA mesothelioma cells and tested for its ability to act as a protective or therapeutic vaccine in a murine tumour model. Vaccine efficacy was assessed by tumour growth/survival of vaccinated mice and FACS analysis used to assess DC maturation and trafficking from vaccine site to draining lymphnodes (dLN). Results: Mice vaccinated prior to tumour challenge with HS lysate induced protection in 40% of mice and caused a significant delay in tumour progression in remaining mice. Vaccine dose-response experiments showed that HS lysate was at least a log more efficient at retarding tumour growth and promoting survival than untreated lysate. HS and untreated lysate were equally effective at maturating DCs, but HS lysate improved trafficking of vaccine-site DCs to draining lymph nodes (dLN). Direct intratumoural injection of HS lysate significantly delayed tumour progression. Conclusions: HS treatment of tumour lysate improved vaccine immunogenicity, was associated with DC maturation, increased DC trafficking to dLNs and delayed tumour growth, particularly when administered intratumourally. Heat shocking autologous tumour cells is a simple and easily translatable approach to generate an immunogenic lysate vaccine with significant prophylactic and therapeutic effects. Coupling intratumoural HS vaccines with conventional therapies such as surgery may improve patient responses for otherwise refractive tumours.