Recombinant GM-CSF plus autologous tumor cells as a vaccine for patients with mesothelioma

Powell, Alex; Creaney, Jenette; Broomfield, Steven; Bruggen, Ivonne van; Robinson, Bruce

doi:10.1016/j.lungcan.2006.01.007

Cited by 45 publications

(29 citation statements)

References 23 publications

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“…This study is provocative, but autologous DC immunotherapy is cumbersome and time consuming, currently limiting this approach to clinical trials in individual centers. An earlier study also used autologous tumor, but administered tumor lysate together with GM-CSF as an adjuvant to 22 patients with mesothelioma [37]. Seven of 22 patients developed humoral immune responses, delayed-type hypersensitivity (DTH) responses, or both, but there were no objective tumor responses observed.…”

Section: Autologous Tumor Vaccinationmentioning

confidence: 99%

Novel Targeted Therapies and Vaccination Strategies for Mesothelioma

Bagia

Nowak

2011

Curr. Treat. Options in Oncol.

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Novel targeted therapies have found a niche in the treatment of many cancers, although the most responsive populations, best biomarkers of response, and appropriate treatment settings are still under investigation. With few exceptions, cancer vaccination strategies have not entered into routine management. In malignant mesothelioma, combination first-line chemotherapy with a platinum and pemetrexed remains the standard of care when systemic therapy is considered. Second-line chemotherapy is used but benefits are uncertain in the absence of appropriately controlled randomized trials. Currently, there are no novel targeted therapies or vaccinations that should be used in this disease outside the context of a clinical trial.

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Section: Autologous Tumor Vaccinationmentioning

confidence: 99%

Novel Targeted Therapies and Vaccination Strategies for Mesothelioma

Bagia

Nowak

2011

Curr. Treat. Options in Oncol.

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“…Our data demonstrates that a simple, inexpensive method of enriching HSP in tumour lysates is comparable to more costly and time consuming autologous lysate preparation methods. Importantly, we have previously demonstrated the feasibility of this preparation method for treating MM [27].…”

Section: Discussionmentioning

confidence: 95%

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

Fisher¹,

Broomfield

Most

et al. 2012

JCT

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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.

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“…45 Histological findings were reviewed treatment. [14][15][16][17] Several studies have also been performed with interferons (IFN) (α, β and γ), and in particular, it has been demonstrated that patients treated with IFNβ have an increased survival, based on the dual action of interferon on both immune and tumor cells. 18 In addition, new and potentially effective treatments have been reported with either the active, where one or several antigens are used for triggering an immune response, or the passive immunotherapy, which relies on effector cells, isolated and activated in vitro before their re-injection in vivo.…”

Section: Resultsmentioning

confidence: 99%