Project 2. Identification and characterisation of novel classes of therapeutically relevant tumour neo-antigens
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Project Leader
Professor Riccardo Dolcetti03 8559 8769
Project Details
Knowledge about the peptide repertoire presented by human leukocyte antigens (HLA) holds the key to unlock target-specific cancer immunotherapies as vaccines and adoptive cell therapies. The recent advances in mass spectrometry approaches have greatly improved our ability to comprehensively characterise the HLA immunopeptidome of tumour cells. However, only a fraction of tumour peptides identified by immunopeptidomics strategies are real immunogenic epitopes able to elicit therapeutically relevant immune responses.
Through the combination of immunopeptidomics and an advanced immunogenicity screening pipeline, this project aims at identifying and characterising novel classes of tumour neo-antigens suitable for therapeutic purposes.
The immunogenicity of the tumour neo-antigens identified will be also validated by detecting specific T-cell responses in the blood of cancer patients, thus paving the way for the development of new immunoassays for improved monitoring of tumour antigen-specific immune responses in patients treated with immunotherapies.
The project will also exploit our nanoparticle-based vaccination platform targeting cross-presenting dendritic cells in vivo to investigate the feasibility and efficacy of vaccination approaches targeting the new antigens identified in suitable humanised mouse models.
Researchers
Professor Riccardo Dolcetti, Project Leader
Dr. Roberta Mazzieri, Senior Scientist
Dr. Bijun Zeng, Senior Post-Doctoral Fellow
Collaborators
Pouya Faridi, Senior Research Fellow, Monash University
Research Opportunities
This research project is available to Honours students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.
Research Publications
Chan JD, von Scheidt B, Zeng B, Oliver AJ, Davey AS, Ali AI, Thomas R, Trapani JA, Darcy PK, Kershaw MH, Dolcetti R, Slaney CY. (2020) Enhancing chimeric antigen receptor T-cell immunotherapy against cancer using a nanoemulsion-based vaccine targeting cross-presenting dendritic cells. Clin Transl Immunology; 9(7):e1157. doi: 10.1002/cti2.1157. PMID: 32704371; PMCID: PMC7374388.
Lam PY, Kobayashi T, Soon M, Zeng B, Dolcetti R, Leggatt G, Thomas R, Mattarollo SR. NKT Cell-Driven Enhancement of Antitumor Immunity Induced by Clec9a-Targeted Tailorable Nanoemulsion. (2019) Cancer Immunol Res; 7(6): 952-962. doi: 10.1158/2326-6066.CIR-18-0650. Epub 2019 May 3. PMID: 31053598.
Zeng B, Middelberg AP, Gemiarto A, MacDonald K, Baxter AG, Talekar M, Moi D, Tullett KM, Caminschi I, Lahoud MH, Mazzieri R, Dolcetti R, Thomas R. (2018). Self-adjuvanting nanoemulsion targeting dendritic cell receptor Clec9A enables antigen-specific immunotherapy. J Clin Invest; 128(5): 1971-1984. doi: 10.1172/JCI96791. Epub 2018 Apr 9. PMID: 29485973; PMCID: PMC5919883.
Montico B, Lapenta C, Ravo M, Martorelli D, Muraro E, Zeng B, Comaro E, Spada M, Donati S, Santini SM, Tarallo R, Giurato G, Rizzo F, Weisz A, Belardelli F, Dolcetti R, Dal Col J. (2017). Exploiting a new strategy to induce immunogenic cell death to improve dendritic cell-based vaccines for lymphoma immunotherapy. Oncoimmunology; 6(11):e1356964. doi: 10.1080/2162402X.2017.1356964. PMID: 29147614; PMCID: PMC5674955.
FaeĢ DA, Martorelli D, Mastorci K, Muraro E, Dal Col J, Franchin G, Barzan L, Comaro E, Vaccher E, Rosato A, Dolcetti R. (2016). Broadening Specificity and Enhancing Cytotoxicity of Adoptive T Cells for Nasopharyngeal Carcinoma Immunotherapy. Cancer Immunol Res; 4(5):431-40. doi: 10.1158/2326- 6066.CIR-15-0108. Epub 2016 Mar 23. PMID: 27009165.