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Microbiology Logo Microbiology & Immunology
Te Tari Moromoroiti me te Ārai Mate

Associate Professor Alexander McLellan


Research interests:

Cancer immunobiology

Current research:

CAR T cells (Chimeric Antigen Receptor-modified T cells) against solid tumours. Cancer stem cell antigens, tumour-associated antigens, and tumour microenvironment metabolites. Cytokine and chemokine receptor strategies to improve T cell function against solid tumours.


Research projects

  • Chimeric Antigen Receptor T cells (CAR-T cells) and NK cells targeting solid tumours
  • Targeting the tumour microenvironment
  • Fighting the cytokine storm
  • Improved anti-cancer T cell migration using targeted cytokines and modified G-protein coupled receptors

MSc and PhD study

We have several PhD projects in the field of immunotherapy available for highly motivated graduate students with graduate-level grades equivalent to The University of Otago grade band: A- to A+. BSc(Hons) and MSc positions are also available. Both international and national students are welcome to apply. For information on MSc and PhD admissions and scholarships visit: http://www.otago.ac.nz/study/masters/index.html ; http://www.otago.ac.nz/study/phd/otago009198.html ; http://www.otago.ac.nz/study/scholarships/otago020695.html.


Lab group         Origin and nationalities of members

                          of our 'lab without borders'

Sarah SaundersonScreen Shot 2017 06 13 at 6.40.45 PM

Postgraduate students

Randy HawAli HosseiniRemy MuhsinAarati PoudelNiki SoniHannah Goy

Current Students

Ali Hosseini PhD student: saRNA and shRNA strategies to improve T cell memory and survival

Remy Muhsin PhD student: Tumour extracellular vesicles in immunotherapy and thrombosis

Aarati Poudel PhD student: Modified G-protein coupled receptors for T cell migration to solid tumours

Tatt Yhew (Randy) Haw: Chimeric antigen receptors (CAR) recognising cancer stem cell antigens

Niki Soni MSc student (year two): Targeting cytokines to the tumour microenvironment

Hannah Goy BSc(Hons): Indirect activation of T cells by targeting CAR-'haptens' to tumour membranes

 

Dr. Sarah Saunderson (Post Doc): CAR constructs targeting tumour enzymes and co-factors

A/Prof. Alex McLellan (Head Chef): Tea and coffee synthesis, grant applications and guidance.

Recently completed

Jessica Bruce-Jones BSc(Hons) student (2016)

Bailey Kennedy BSc(Hons) student (2015)


Other activities

Member of the Centre for Translational Cancer Research (Otago) and The Renal Theme (Otago). Former Manager, University of Otago Flow Cytometry Facility (2004-2012)


Current Collaborations

  • Dr. Yoshio Nakatani; Dept. Microbiology and Immunology (From the stairwell to the world: 2017 Proof of Concept winners named)
  • Assoc. Prof. Mike Kershaw and Assoc. Prof. Phil Darcy; Peter MacCallum Cancer Centre, Melbourne, Australia
  • Prof. Mette Rosenkilde / Dr. Stefanie Karlshøj; University of Copenhagen, Denmark): GPCR and the tumour microenvironment in T cell immunotherapy

Sources of funding 

The group has recently received funding from HRC (2017 Explorer grant), The Proof of Concept Award (cytokine storm and tumour immunotherapy), The Cancer Society, The William Sherriff Trust, Lottery Health Research, The University of Otago Research Grant committee and the Otago School of Medical Sciences.


Recent publicity


 

Publications:

 

Selected publications (see Google Scholar or PubMed profile)

Muhsin-Sharafaldine MR, Saunderson SC, Dunn AC, McLellan AD. Melanoma growth and lymph node metastasis is independent of host CD169 expression. Biochem Biophys Res Commun. 2017 Mar 27. pii: S0006-291X(17)30613-7.

Muhsin-Sharafaldine R-M, Kennedy BR, Saunderson SC, Buchanan CR, Dunn AC, Faed JM, McLellan AD. Mechanistic insight into the procoagulant activity of tumor-derived apoptotic vesicles. Biochimica Biophysica Acta – General Subjects. 2017 Feb;1861(2):286-295

Muhsin-Sharafaldine R-M, Saunderson SC, Dunn AC, Faed JM, Kleffmann T, McLellan AD. Procoagulant and immunogenic properties of melanoma exosomes, microvesicles and apoptotic vesicles. Oncotarget. 2016. doi: 10.18632/oncotarget.10783.

Jemon K, Leong CM, Ly K, Young SL, McLellan AD, Hibma MH. Suppression of the CD8 T cell response by human papillomavirus type 16 E7 occurs in Langerhans cell-depleted miceScientific Reports. 2016 Oct 6;6:34789. doi: 10.1038/srep34789.

Black LV*, Saunderson SC*, Coutinho FP, Muhsin-Sharafaldine MR, Damani TT, Dunn AC, McLellan AD. The CD169 sialoadhesin molecule mediates cytotoxic T cell responses to tumour apoptotic vesicles. Immunol Cell Biol. 2015 Dec 9. doi:10.1038/icb.2015.111. *First equal authorship.

Dunn E, Roxburgh M, Larsen L, Smith RA, McLellan AD, Heikal AF. Murphy MP, Cook GM. Incorporation of triphenylphosphonium functionality improves the inhibitory properties of phenothiazine derivatives in Mycobacterium tuberculosis. Bioorganic and Medicinal Chemistry 2014. 22(19):5320-8

McLellan AD. Can microbes destroy cancer? Australasian Science, 2014; Sept.: 19-21.

McLellan AD. A critical role for natural killer cells in tumour immunotherapy. Oncoimmunlogy 2014. 2014; 3:e28582; http://dx.doi.org/10.4161/onci.28582

Bouwer AL, Saunderson SC, Caldwell FJ, Damani TT, Pelham SJ, Dunn AC, Jack RW, Stoitzner P, McLellan AD. Natural killer cells are required for dendritic cell-based immunotherapy at the time of tumor challenge. Journal of Immunology 2014. doi:10.4049/jimmunol.1202797

Saunderson SC, Dunn AC, Crocker PR, McLellan AD. CD169 mediates the capture of exosomes in spleen and lymph nodeBlood. 2014. 123:208-216.

Tannock GW, Taylor C, Lawley B, Loach, Gould, M, Dunn AC, McLellan AD, Black MA, McNoe L, Dekker J, Gopal P, Collet MA. Altered transcription of murine genes induced in the small bowel by administration of probiotic strain Lactobacillus rhamnosus HN001Appl Environ Microbiol. 2014. 80(9):2851-9.

Bouwer AL, Saunderson SC, Dunn AC, Lester KL, Crowley LR, Jack RW,  McLellan AD. Rapid interferon-gamma release from natural killer cells induced by a streptococcal commensalJournal of Interferon & Cytokine Research. 2013. 33(8):459-66.

Czepluch W, Dunn AC, Everitt CL, Dorer D, Saunderson SC, Aldwell FE, McLellan AD. Extracellular forms of Mycobacterium bovis BCG in the mucosal lymphatic tissues following oral vaccination. Int. J. Mycobacteriology. 2012 2(1) 44–50. http://dx.doi.org/10.1016/j.ijmyco.2012.11.004.

Ting YT, Coates PT, Walker RJ, McLellan AD. Urinary tubular biomarkers as potential early predictors of renal allograft rejectionNephrology. 2012; 17(1):11-6.

Baker NJ, Schofield JC, Caswell MD, McLellan AD. An Investigation of Early Atipamezole Reversal of Medetomidine / Ketamine Anesthetised MiceJ. Am. Assoc. Lab. Anim. Sci. 2011; 50(6):916-20.

Nixon G, Blattner K, Dawson J, Dovey S, Black M, Wilkins G, Dunn AC, McLellan AD. Streptokinase antibodies in patients presenting with acute coronary syndrome in three rural New Zealand populations.Journal of Clinical Pathology 2011; 64(5):426-9.

Ting YT, Coates PT, Marti HP, Dunn AC, Parker RM, Pickering JW, Jack RW, Kemp RA, Walker RJ, McLellan AD. Urinary soluble HLA-DR is a potential biomarker for acute renal transplant rejection.Transplantation 2010; 89(9):1071-8.

Temme S, Eis-Hübinger A, McLellan AD, Koch N. The Herpes Simplex Virus-1 Encoded Glycoprotein B Diverts HLA-DR Into the Exosome PathwayJ. Immunol. 2010; 184: 236-43.

Stoitzner P, Romani N, McLellan AD, Tripp CH, Ebner S. Isolation of skin dendritic cells from mouse and manMethods Mol Biol. 2010: 595:235-48.

Bouwer AL, Netter P, Kemp RA and McLellan AD. A defined serum-free medium useful for monitoring anti-melanoma responses induced by dendritic cell immunotherapy. J. Immunological Methods. 2009; 352: 178-181.

Ting YT, Temme S, Koch N, McLellan AD. A new monoclonal antibody recognizing a linear determinant on the HLA-DR-chain N-terminusHybridoma 2009; 28: 423-9.

McLellan AD. Exosome release by primary B cellsCritical Reviews in Immunology. 2009; 29(3) 203-217.

Gebhard S, Hümpel A, McLellan AD and Cook GM. The alternative sigma factor SigF of Mycobacterium smegmatis is required for survival of heat shock, acidic pH and oxidative stress.Microbiology-SGM. 2008; 154: 2786-95.

Saunderson SC, Schuberth PC, Miller, L, Hock, BD, Dunn, AC, MacKay, PA, Jack, RW, Koch N. and McLellan AD. Induction of exosome release in primary B cells stimulated via CD40 and the IL-4 receptorJournal of Immunology. 2008; 180(12):8146- 52.

Koch N, McLellan AD, Neumann J. A revised model for invariant chain-mediated assembly of Major Histocompatibility Complex class II peptide receptorsTrends in Biochemical Sciences 2007;32(12):532-7.

Dorer DE, Czepluch W, Lambeth MR, Dunn AC, Reitinger C, Aldwell FE, McLellan AD. Lymphatic tracing and T cell responses following oral vaccination with live Mycobacterium bovis (BCG)CellularMicrobiology. 2007; 9(2): 544-553.

O'Donnell J, Hayman M, Spellerberg M, McLellan AD; Brooksbank K, Chapman P, Stamp L.Antineutrophil cytoplasmic antibody measurement - advantages and disadvantages of a capture PR3 ELISA and a direct PR3 ELISA. Pathology 2007; 39(2):258-63.

MacKay PA, Leibundgut-Landmann S, Koch N, Dunn AC, Reith W, Jack RW, McLellan AD. Circulating, soluble forms of major histocompatability complex antigens are not exosome-associated. European Journal of Immunology 2006; 36(11):2875- 2884.

Douillard P, Stoitzner P, Tripp CH, Clair-Moninot V, Ait-Yahia S, McLellan AD, Eggert A, Romani N, and Saeland S. Mouse lymphoid tissue contains distinct subsets of langerin / CD207+ dendritic cells, only one of which represents epidermal-derived Langerhans cells. Journal of Investigative Dermatology. 2005; 125(5):983-94.

Aldwell FE, Baird MA, Fitzpatrick CE, McLellan AD., Cross F, Lambeth M, and Buchan GS Oral vaccination of mice with lipid-encapsulated Mycobacterium bovis BCG: Anatomical sites of bacterial replication and immune activity. Immunology and Cell Biology. 2005; 83(5):549-53.

Hock BD, Roberts G, McKenzie JL, Gokhale P, Salm N, McLellan AD, Patton N, Roake JA. Exposure to the electrofusion process can increase the immunogenicity of human cells. Cancer Immunology and Immunotherapy. 2005; 54:880-890.

Leverkus M, McLellan AD, Heldmann M, Eggert AO, Brocker EB, Koch N, Kampgen E. MHC class II-mediated apoptosis in dendritic cells: a role for membrane-associated and mitochondrial signaling pathways. Int Immunol. 2003; 15(8):993-1006.

Kammerer U, Eggert AO, Kapp M, McLellan AD, Geijtenbeek TB, Dietl J, VanKooyk Y, Kampgen E.Unique Appearance of Proliferating Antigen-Presenting Cells Expressing DC-SIGN(CD209) in the Decidua of Early Human Pregnancy. Am J Pathol. 2003; 162(3):887-96.

Stoitzner P, Holzmann S, McLellan AD, Ivarsson L, Stossel H, Kapp M,Kammerer U, Douillard P, Kampgen E, Koch F, Saeland S, Romani N. Visualization and characterization of migratory Langerhans cells in murine skin and lymph nodes by antibodies against Langerin/CD207. J Invest Dermatol. 2003; 120(2):266-74.

McLellan AD, Kapp M, Eggert A, Linden C, Bommhardt U, Brocker EB, Kammerer U, Kampgen E.Anatomic location and T-cell stimulatory functions of mouse dendritic cell subsets defined by CD4 and CD8 expression. Blood. 2002; 99(6):2084-93.

Kolb-Maurer A, Pilgrim S, Kampgen E, McLellan AD, Brocker EB, Goebel W,Gentschev I. Antibodies against listerial protein 60 act as an opsonin for phagocytosis of Listeria monocytogenes by human dendritic cells. Infect Immun. 2001; 69(5):3100-9.

Schrama D, thor Straten P, Fischer WH, McLellan AD, Brocker EB, Reisfeld RA, Becker JC. Targeting of lymphotoxin-alpha to the tumor elicits an efficient immune response associated with induction of peripheral lymphoid-like tissue. Immunity. 2001; 14(2):111-21.

McLellan AD, Terbeck G, Mengling T, Starling GC, Kiener PA, Gold R, Brocker EB, Leverkus M, Kampgen E. Differential susceptibility to CD95 (Apo-1/Fas) and MHC class II-induced apoptosis during murine dendritic cell development. Cell Death Differ. 2000; 7(10):933-8.

McLellan AD, Brocker EB, Kampgen E. Dendritic cell activation by danger and antigen-specific T-cell signalling. Exp Dermatol. 2000; 9(5):313-22.

McLellan A, Heldmann M, Terbeck G, Weih F, Linden C, Brocker EB, Leverkus M, Kampgen E. MHC class II and CD40 play opposing roles in dendritic cell survival. Eur J Immunol. 2000; 30(9):2612-9.

McLellan AD, Kampgen E. Functions of myeloid and lymphoid dendritic cells. Immunol Lett. 2000; 72(2):101-5.

McLellan AD, Heiser A, Hart DN. Induction of dendritic cell costimulator molecule expression is suppressed by T cells in the absence of antigen-specific signalling: role of cluster formation, CD40 and HLA-class II for dendritic cell activation. Immunology. 1999; 98(2):171-80.

McLellan AD, Heiser A, Sorg RV, Fearnley DB, Hart DN. Dermal dendritic cells associated with T lymphocytes in normal human skin display an activated phenotype. J Invest Dermatol. 1998; 111(5):841-9.

McLellan AD, Sorg RV, Williams LA, Hart DN. Human dendritic cells activate T lymphocytes via a CD40: CD40 ligand-dependent pathway. Eur J Immunol. 1996; 26(6):1204-10.

Starling GC, McLellan AD, Egner W, Sorg RV, Fawcett J, Simmons DL, Hart DN. Intercellular adhesion molecule-3 is the predominant co-stimulatory ligand for leukocyte function antigen-1 on human blood dendritic cells. Eur J Immunol. 1995;2 5(9):2528-32.

McLellan AD, Starling GC, Williams LA, Hock BD, Hart DN. Activation of human peripheral blood dendritic cells induces the CD86 co-stimulatory molecule. Eur J Immunol. 1995; 25(7):2064-8.

McLellan AD, Starling GC, Hart DN. Isolation of human blood dendritic cells by discontinuous Nycodenz gradient centrifugation. J Immunol Methods. 1995,184:81-9.