Sir Peter MacCallum Department of Oncology - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/274

Filters

2020 - 2021 2
2
Reset filters

Settings
Statistics
Citations
Author: Darcy, Phillip × Author: Kershaw, Michael × Author: Oliver, Amanda × Author: Trapani, Joseph × End date: 2021 × Start date: 2020 ×

Search Results

Now showing 1 - 2 of 2
  • Item
    Thumbnail Image
    Cross-talk between tumors at anatomically distinct sites
    Oliver, AJ ; Darcy, PK ; Trapani, JA ; Kershaw, MH ; Slaney, CY (WILEY, 2021-01)
    Cancer tissue is not homogenous, and individual metastases at different anatomical locations can differ from the primary tumor and from one another in both their morphology and cellular composition, even within an individual patient. Tumors are composed of cancer cells and a range of other cell types, which, together with a variety of secreted molecules, collectively comprise the tumor microenvironment (TME). Cells of the TME can communicate with each other and with distant tissues in a form of molecular cross-talk to influence their growth and function. Cross-talk between cancer cells and local immune cells is well described and can lead to the induction of local immunosuppression. Recently, it has become apparent that tumors located remotely from each other, can engage in cross-talk that can influence their responsiveness to various therapies, including immunotherapy. In this article, we review studies that describe how tumors systemically communicate with distant tissues through motile cells, extracellular vesicles, and secreted molecules that can affect their function. In addition, we summarize evidence from mouse studies and the clinic that indicate an ability of some tumors to influence the progression and therapeutic responses of other tumors in different anatomical locations.
  • Item
    Thumbnail Image
    Enhancing chimeric antigen receptor T-cell immunotherapy against cancer using a nanoemulsion-based vaccine targeting cross-presenting dendritic cells
    Chan, JD ; von Scheidt, B ; Zeng, B ; Oliver, AJ ; Davey, AS ; Ali, A ; Thomas, R ; Trapani, JA ; Darcy, PK ; Kershaw, MH ; Dolcetti, R ; Slaney, CY (WILEY, 2020)
    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 Clec9A-TNE could prime DCs for antigen presentation to CAR T cells through TCRs and thus improve CAR T-cell responses against solid tumours. To test this hypothesis, we used CAR T cells expressing transgenic TCRs specific for ovalbumin (OVA) peptides SIINFEKL (CAROTI) or OVA323-339 (CAROTII). RESULTS: We demonstrated that the Clec9A-TNEs encapsulating full-length recombinant OVA protein (OVA-Clec9A-TNE) improved CAROT T-cell proliferation and inflammatory cytokine secretion in vitro. Combined treatment using the OVA-Clec9A-TNE and CAROT cells resulted in durable responses and some rejections of tumours in immunocompetent mice. Tumour regression was accompanied by enhanced CAROT cell proliferation and infiltration into the tumours. CONCLUSION: Our study presents Clec9A-TNE as a prospective avenue to enhance CAR T-cell efficacy for solid cancers.