BSc(Hons) (Otago), MSc(Distinc) (Otago), PhD(Vuw)
Overseeing the Malaghan Institute's current involvement in the cancer vaccine trials is Assoc Prof Ian Hermans, Head of the Vaccine Research group. Assoc Prof Hermans studied dendritic cell-based vaccination with Prof Ronchese at the Malaghan Institute between 1995 and 2001, before taking up a position at the Tumour Immunology Unit, Weatherall Institute of Molecular Medicine, at the University of Oxford, UK. In 2005 Assoc Prof Hermans returned to the Malaghan Institute and was awarded a Sir Charles Hercus Research Fellowship from the Health Research Council of New Zealand to pursue his research into improving the potency and efficacy of vaccines by exploiting the activity of NKT cells. His group has shown that NKT cells have the capacity to directly enhance the function of dendritic cells, and thus indirectly influence the quality of the whole immune response.
The overall goal of my research is to design more effective vaccines against diseases such as cancer. It is known that white blood cells called T cells can kill tumour cells. Vaccines that induce the activity of T cells therefore hold considerable promise as new therapeutic agents.
We are looking at the specific immune cell populations involved in eliciting effective immune responses to vaccination, including the dendritic cells responsible for stimulating T cells, and other less well-known cells such as Natural Killer T (NKT) cells that contribute to the induced response. Working together with chemists, we are aiming to define compounds that can be incorporated into vaccines to ensure optimum, coordinated activity of all of the immune cells involved.
We are also exploring how other therapies for cancer, such as chemotherapy, radiation and hyperthermia, affect the immune system, with a view to combining these therapies with vaccination.
We work closely with New Zealand leaders in the fields of immunology, medicinal chemistry and clinical oncology to test our vaccines in cancer patients.
Contributors: Taryn Osmond, Dr Troels Petersen, Dr Ian Hermans
Researchers at the Malaghan Institute and the Wellington Blood and Cancer Centre, have undertaken extensive pre-clinical and clinical analyses of vaccines based on the injection of dendritic cells that have been loaded with tumour derived material as a source of antigens. Dendritic cells belong to a subset of cells called antigen-presenting cells that take up and process molecules from the extracellular environment. The dendritic cells then present this information to other cells of the immune system, such as cytotoxic (CD8+) T cells, in a manner that stimulates immunity.
Recent studies have identified a specific subset of langerin-expressing dendritic cells in the spleen as critical for the induction of cytotoxic T cell activity. Using a mouse strain in which langerin-expressing dendritic cells can be depleted, PhD student Taryn Osmond is examining the in vivo function of these cells in more detail. The information generated from her research will help define how best to exploit the activity of different dendritic cell populations to optimise vaccination strategies for cancer therapy.
This research is supported by: the Cancer Society of New Zealand, the Health Research Council of New Zealand and The Royal Society of New Zealand Marsden Fund.
Contributors: Mr Martin Hunn, Evelyn Bauer, Catherine Wood, Dr Ian Hermans, collaborating with Dr David Hamilton, Marina Dzhelali (CCDHB) and Prof Michael Findlay (CTNZ)
In late 2008 the Malaghan Institute initiated a Phase I clinical trial in collaboration with the Capital & Coast District Health Board to test the feasibility and safety of using dendritic cell vaccines in combination with temozolomide chemotherapy for the treatment of patients with recurrent glioblastoma multiforme, a highly aggressive brain tumour with a 100% fatality rate. This trial has recently been completed, the outcomes from which are currently being analysed and prepared for publication.
Personalised vaccines, such as those being used in the glioblastoma multiforme clinical trial, are very intensive to produce but they do offer a broad immunity that recognises the unique features of an individual patient's tumour tissue. Complementing the clinical trials is an extensive basic immunology research programme involving several of the Institute's research groups, aimed at understanding anti-tumour immune responses and how they can be more effectively elicited with vaccines.
Cheong S, Ferguson P, Hermans IF, Jameson GNL, Prabakar S, Herman DAJ, Tilley RD (2012) Synthesis and stability of highly crystalline and stable iron/iron oxide core/shell nanoparticles for biomedical applications. ChemPlusChem, 77:135-40
Dangerfield EM, Cheng JM, Knight DA, Weinkove R, Dunbar PR, Hermans IF, Timmer MS, Stocker BL (2012) Species-specific activity of glycolipid ligands for invariant NKT cells. Chembiochem, 13:1349-56
Dickgreber N, Farrand KJ, van Panhuys N, Knight DA, McKee SJ, Chong ML, Miranda-Hernandez S, Baxter AG, Locksley RM, Le Gros G, Hermans IF (2012) Immature murine NKT cells pass through a stage of developmentally programmed innate IL-4 secretion. J Leukoc Biol, [Epub ahead of print]
Hunn MK, Farrand KJ, Broadley KW, Weinkove R, Ferguson P, Miller RJ, Field CS, Petersen T, McConnell MJ, Hermans IF Vaccination with irradiated tumor cells pulsed wtih an adjuvant that stimulates NKT cells is an effective treatment for glioma. Clin Cancer Res, 2012 Nov 12 [Epub ahead of print]
McKee SJ, Young VL, Clow F, Hayman CM, Baird MA, Hermans IF, Young SL, Ward VK (2012) Virus-like particles and α-galactosylceramide form a self-adjuvanting composite particle that elicits anti-tumour immune responses. J Control Release, 159:338-45
Weinkove R, Brooks CR, Carter JM, Hermans IF, Ronchese F (2012) Functional invariant natural killer T cell and CD1d axis in chronic lymphocytic leukemia: implications for immunotherapy. Haematologica [Epub ahead of print]
Ainge GD, Martin WJ, Compton BJ, Hayman CM, Larsen DS, Yoon S-i, Wilson IA, Harper JL, Painter GF (2011) Synthesis and toll-like receptor 4 (TLR4) activity of phosphatidylinositol dimannoside analogues. J Med Chem, 54:7268-79
Broadley KW, Hunn MK, Farrand KJ, Price KM, Grasso C, Miller RJ, Hermans IF, McConnell MJ (2011) Side population is not necessary or sufficient for a cancer stem cell phenotype in glioblastoma multiforme. Stem Cells, 29:452-61
Cheng JM, Chee SH, Knight DA, Acha-Orbea H, Hermans IF, Timmer MS, Stocker BL (2011) An improved synthesis of danyslated alpha-galactosylceramide and its use as a fluorescent probe for the monitoring of glycolipid uptake by cells. Carbohydr Res, 346:914-26
Cheong S, Ferguson P, Feindel KW, Hermans IF, Callaghan PT, Meyer C, Slocombe A, Su CH, Cheng FY, Yeh CS, Ingham B, Toney MF, Tilley RD (2011) Simple synthesis and functionalization of iron nanoparticles for magnetic resonance imaging. Angew Chem Int Ed Engl, 50:4206-9
Girvan RC, Knight DA, O'Loughlin CJ, Hayman CM, Hermans IF, Webster GA (2011) MIS416, a non-toxic microparticle adjuvant derived from Propionibacterium acnes comprising immunostimulatory muramyl dipeptide and bacterial DNA promotes cross-priming and Th1 immunity. Vaccine, 29:545-57
Herman DA, Ferguson P, Cheong S, Hermans IF, Ruck BJ, Allan KM, Prabakar S, Spencer JL, Lendrum CD, Tilley RD (2011) Hot-injection synthesis of iron/iron oxide core/shell nanoparticles for T(2) contrast enhancement in magnetic resonance imaging. Chem Commun (Camb), 47:9221-3
Petersen TR, Sika-Paotonu D, Knight DA, Simkins HM, Hermans IF (2011) Exploiting the role of endogenous lymphoid-resident dendritic cells in the priming of NKT cells and CD8+ T cells to dendritic cell-based vaccines. PLoS One, 6:e17657
Simkins HM, Hyde E, Farrand KJ, Ong ML, Degli-Esposti MA, Hermans IF, Ronchese F (2011) Administration of alpha-galactosylceramide impairs the survival of dendritic cell subpopulations in vivo. J Leukoc Biol, 89:753-62
Brooks CR, Weinkove R, Hermans IF, van Dalen CJ, Douwes J (2010) Invariant natural killer T cells and asthma: immunologic reality or methodologic artifact? J Allergy Clin Immunol, 126:882-5
Petersen TR, Dickgreber N, Hermans IF (2010) Tumor antigen presentation by dendritic cells. Crit Rev Immunol, 30:345-86. Review.
Petersen TR, Sika-Paotonu D, Knight DA, Dickgreber N, Farrand KJ, Ronchese F, Hermans IF (2010) Potent anti-tumour responses to immunization with dendritic cells loaded with tumor tissue and an NKT cell ligand. Immunol Cell Biol, 88:596-604
Dickgreber N, Stoitzner P, Bai Y, Price KM, Farrand KJ, Manning K, Angel CE, Dunbar PR, Ronchese F, Fraser JD, Bäckström BT, Hermans IF (2009) Targeting antigen to MHC class II molecules promotes cross-presentation and enhances immunotherapy. J Immunol, 182:1260-9
Farrand KJ, Dickgreber N, Stoitzner P, Ronchese F, Petersen TR, Hermans IF (2009) Langerin+CD8alpha+ dendritic cells are critical for cross-priming and IL-12 production in response to systemic antigens. J Immunol, 183:7732-42
Tripp CH, Sparber F, Hermans IF, Romani N, Stoitzner P (2009) Glycolipids injected into the skin are presented to NKT cells in the draining lymph node independently of migratory skin dendritic cells. J Immunol, 182:7644-54
Andrew KA, Simkins HMA, Witzel S, Perret R, Hudson J, Hermans IF, Ritchie DS, Yang J, Ronchese F (2008) Dendritic cells treated with lipopolysaccharide up-regulate serine protease inhibitor 6 and remain sensitive to killing by cytotoxic T lymphocytes in vivo. J Immunol, 181:8356-62
Stoitzner P, Green LK, Jung JY, Price KM, Tripp CH, Malissen B, Kissenpfennig A, Hermans IF, Ronchese F (2008) Tumor immunotherapy by epicutaneous immunization requires Langerhans cells. J Immunol, 180:1991-8
Hermans IF, Silk JD, Gileadi U, Masri SH, Shepherd D, Farrand KJ, Salio M, Cerundolo V (2007) Dendritic cell function can be modulated through the cooperative actions of TLR ligands and invariant NKT cells. J Immunol, 178:2721-9
Matthews KE, Qin JS, Yang J, Hermans IF, Palmowski MJ, Cerundolo V, Ronchese F (2007) Increasing the survival of dendritic cells in vivo does not replace the requirement for CD4+ T cell help during primary CD8+ T cell responses. J Immunol, 179:5738-47
Lee A, Farrand KJ, Dickgreber N, Hayman CM, Jürs S, Hermans IF, Painter GF (2006) Novel synthesis of -galactosyl ceramides and confirmation of their powerful NKT cell agonist activity. Carbohydrate Research 341: 2785-2798
Matthews KE, Hermans IF, Roberts JM, Ching LM, Ronchese F (2006) 5,6-Dimethylxanthenone-4-acetic acid treatment of a non-immunogenic tumour does not synergize with active or passive CD8+ T-cell immunotherapy. Immunol Cell Biol, 84:383-9
Yang J, Huck SP, McHugh RS, Hermans IF, Ronchese F (2005) Perforin-dependent elimination of dendritic cells regulates the expansion of antigen-specific CD8+ T cells in vivo. Proc Natl Acad Sci USA, 103:147-52
Silk JD, Hermans IF, Gileadi U, Chong TW, Shepherd D, Salio M, Mathew B, Schmidt RR, Lunt SJ, Williams KJ, Stratford IJ, Harris AL, Cerundolo V (2004) Utilizing the adjuvant properties of CD1d-dependent NK T cells in T cell-mediated immunotherapy. J Clin Invest, 114:1800-11
Ritchie DS, Yang J, Hermans IF, Ronchese F (2004) B-Lymphocytes activated by CD40 ligand induce an antigen-specific anti-tumour immune response by direct and indirect activation of CD8(+) T-cells. Scand J Immunol, 60:543-51
Salio M, Palmowski MJ, Atzberger A, Hermans IF, Cerundolo V (2004) CpG-matured murine plasmacytoid dendritic cells are capable of in vivo priming of functional CD8 cell responses to endogenous but not exogenous antigens. J Exp Med, 199:567-79
Hermans IF, Silk JD, Yang J, Palmowski MJ, Gileadi U, McCarthy C, Salio M, Ronchese F, Cerundolo V (2004) The VITAL assay: a versatile fluorometric technique for assessing CTL- and NKT-mediated cytotoxicity against multiple targets in vitro and in vivo. J Immunol Methods, 285:25-40
Cerundolo V, Hermans IF, Salio M (2004) Dendritic cells: a journey from laboratory to clinic. Nat Immunol, 5:7-10
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