Enhancing chimeric antigen receptor T-cell immunotherapy against cancer using a nanoemulsion-based vaccine targeting cross-presenting dendritic cells

Jack D Chan; Bianca von Scheidt; Bijun Zeng; Amanda J Oliver; Ashleigh S Davey; Aesha Ali; Ranjeny Thomas; Joseph A Trapani; Phillip K Darcy; Michael H Kershaw; Riccardo Dolcetti; Clare Y Slaney

Journal article

Enhancing chimeric antigen receptor T-cell immunotherapy against cancer using a nanoemulsion-based vaccine targeting cross-presenting dendritic cells

Jack D Chan, Bianca von Scheidt, Bijun Zeng, Amanda J Oliver, Ashleigh S Davey, Aesha Ali, Ranjeny Thomas, Joseph A Trapani, Phillip K Darcy, Michael H Kershaw, Riccardo Dolcetti, Clare Y Slaney

Clinical and Translational Immunology | WILEY | Published : 2020

DOI: 10.1002/cti2.1157

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Abstract

Objectives: Adoptive transfer of chimeric antigen receptor (CAR)-modified T cells is a form of cancer immunotherapy that has achieved remarkable efficacy in patients with some haematological cancers. However, challenges remain in CAR T-cell treatment of solid tumours because of tumour-mediated immunosuppression. Methods: We have demonstrated that CAR T-cell stimulation through T-cell receptors (TCRs) in vivo can generate durable responses against solid tumours in a variety of murine models. Since Clec9A-targeting tailored nanoemulsion (Clec9A-TNE) vaccine enhances antitumour immune responses through selective activation of Clec9A+ cross-presenting dendritic cells (DCs), we hypothesised that ..

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University of Melbourne Researchers

Phillip Darcy Author The Sir Peter MacCallum Department of Oncology

Clare Slaney Author The Sir Peter MacCallum Department of Oncology

Michael Kershaw Author The Sir Peter MacCallum Department of Oncology

Joseph Trapani Author The Sir Peter MacCallum Department of Oncology

Riccardo Dolcetti Author Microbiology and Immunology

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Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia

Awarded by National Breast Cancer Foundation (NBCF) of Australia

Awarded by Susan G. Komen Breast Cancer Foundation

Awarded by Cancer Council Queensland

Funding Acknowledgements

This work was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (1103352 and 1176935) the National Breast Cancer Foundation (NBCF) of Australia (IIRS-18-047, IIRS-18-064 and IIRS-20-073), Susan G. Komen Breast Cancer Foundation (16376637) and Cancer Council Queensland (1145758 and 1165064). PKD was supported by a Principal Research Fellowship from the NHMRC. CYS was supported by a Postdoctoral Fellowship from the NBCF. JAT is a Rosie Lew Fellow of the Peter MacCallum Cancer Foundation.