Research: Pre-clinical testing of new CAR T cells and CAR NK cells in NSG mice. Building high-efficiency lentivirus, retrovirus and transposon gene transfer systems. Genetic designs for internal control of anti-cancer T cells and NK cells, including inducible promoters and bi-directional (dual CAR or CAR + payload) designs. Optimised expansion protocols for CAR NK cells, including kitsets for constructing artificial antigen presenting cells.
Teaching and research support: Graduate and undergraduate teaching portfolios in Immunology, Medicine, Medical Laboratory Science, Microbiology and Pharmaceutical Sciences, including lab-based teaching. Divisional Course Approver. Experience in Animal Ethics as Committee member for nine years. Current Chair of Bioimager Acquisition Committee and former Chair of Flow Cytometry facility.
Cancer immunotherapy
CAR T cells (Chimeric Antigen Receptor-modified T cells) against solid tumours. Dual CAR T cells using bi-directional promoters, tumour-micro-environment sensors and CAR T cell metabolism boosting with coding and non-coding RNA. Cytokine and chemokine receptor strategies to improve T cell function against solid tumours.
Mclellan Lab 2020
Prof. Alex Mclellan
Principal Investigator
alex.mclellan@otago.ac.nz
Office: +64 3 479 7728
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| Dr. Sarah Saunderson - Research Fellow | TBA - Post Doctoral Fellow | |||
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| Thiloma Liyanage - Assistant Research Fellow | ||||
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| Sam Smith-Bell - PhD Student | |||
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| Lachie Dobson -PhD student | |||
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| Tom McDermott - BSc(Hons) GENE |
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| Blake Sluyter - BSc(Hons) |
The group has recently received funding from HRC (2020 & 2017 Explorer grant), The Royal Society Marsden Fund (2019), The NZ Cancer Society 2018, The Proof of Concept Award (2017; cytokine storm and tumour immunotherapy), The William Sherriff Trust, Lottery Health Research, The University of Otago Research Grant committee and the Otago School of Medical Sciences. In 2014, a generous donation of $4500 from Audrey Tay's 'Shave for Cancer' supported our work on cancer-related thrombosis – thanks Audrey! http://www.otago.ac.nz/ctcr/news/otago072972.html
Hosseini Rad SM, Wannigama DL , Hirankarn N and McLellan AD The impact of the SARS-CoV-2 non-synonymous mutations on miRNA binding sites. Scientific Reports 2023. 13, 16945.
Dobson LJ, Saunderson SC, Smith-Bell SW, and McLellan AD. Sleeping Beauty kit sets provide rapid and accessible generation of artificial antigen-presenting cells for natural killer cell expansion. Immunology and Cell Biology. 2023. 2023, Vol.101(9), p.847-856
Tan GMY, Poudel A, Rad SM AH, and McLellan AD. Anti-apoptotic c-FLIP reduces the anti-tumour activity of chimeric antigen receptor (CAR) T cells. Cancers 2022, 14(19), 4854; https://doi.org/10.3390/cancers14194854
*Saunderson SC, Rad SMAH, McLellan AD. Noise-reduction and sensitivity-enhancement of a Sleeping 2 Beauty-based Tet-On system. Genes 2022, 13(10), 1679. *Corresponding author.
*Hosseini-Rad SMAH, Halpin JC, Tawinwung S, Suppipat K, Hirankarn N, McLellan AD. MicroRNA-mediated metabolic reprogramming of chimeric antigen receptor T cells. Immunology and Cell Biology 2022. doi: 10.1111/imcb.12551. *Corresponding author.
*White LG, Goy HE,Rose AJ, McLellan, A.D. Controlling Cell Trafficking: Addressing Failures in CAR T and NK Cell Therapy of Solid Tumours. Cancers 2022, 14, 978. https://doi.org/10.3390/cancers14040978. *Corresponding author.
*Rad SMAH, *Halpin JC, Mollaei M, Smith-Bell SWJ, Hirankarn N, McLellan AD. Metabolic and Mitochondrial functioning in Chimeric Antigen Receptor (CAR) – T cells. Cancers. 2021. 13(6), 1229. *Joint first authors.
He, K, Rad, S.A.H, Poudel A, McLellan, A.D. Compact Bidirectional Promoters for Dual-Gene Expression in a Sleeping Beauty Transposon. International Journal of Molecular Sciences. 2020; 21(23), 9256.
Rad SM AH, Poudel A, Tan GMY, He K and McLellan AD. Regulation of Human Mcl-1 by a Divergently-Expressed Antisense Transcript. Gene. 2020. https://doi.org/10.1016/j.gene.2020.145016
Rad SM AH, Poudel A, Tan GMY, and McLellan AD. Promoter choice: who should drive the CAR in T Cells? Plos One 2020. 15(7):e0232915. doi: 10.1371/journal.pone.0232915.
Rad SM AH, Poudel A, Tan GMY, and McLellan AD. Optimisation of Tet-On inducible systems for Sleeping Beauty-based chimeric antigen receptor (CAR) applications. Scientific Reports 2020. 10:13125. https://doi.org/10.1038/s41598-020-70022-0
Rad SM AH, and McLellan AD. Implications of SARS-CoV-2 mutations for genomic RNA structure and host microRNA targeting. International Journal of Molecular Sciences. 2020; 21(13), 4807
McLellan AD, Rad SM. Chimeric antigen receptor T cell persistence and memory cell formation. Immunology and Cell Biology. 2019. doi: 10.1111/imcb.12254.
Weinkove R, George P, Dasyam N. McLellan AD. Selecting costimulatory domains for CAR T cells: functional and clinical considerations. Clinical Translational Immunology. 2019. May 11;8(5):e1049. doi: 10.1002/cti2.1049. Winner of the ASI Social Impact Prize.
Muhsin-Sharafaldine MR and McLellan AD. Apoptotic vesicles: Deathly players in cancer-associated coagulation. Immunology and Cell Biology. 2018. doi: 10.1111/imcb.12162
Muhsin-Sharafaldine MR and McLellan AD. Tumor-derived apoptotic vesicles: with death they do part. Frontiers in Immunology 2018. doi: 10.3389/fimmu.2018.00957
Saunderson SC and McLellan AD. Role of lymphocyte subsets in the immune response to primary B cell-derived exosomes. Journal of Immunology
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 MR, 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 MR, 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 mice. Scientific 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 node. Blood. 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 HN001. Appl 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 commensal. Journal 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 rejection. Nephrology. 2012; 17(1):11-6.
Baker NJ, Schofield JC, Caswell MD, McLellan AD. An Investigation of Early Atipamezole Reversal of Medetomidine / Ketamine Anesthetised Mice. J. 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 Pathway. J. Immunol. 2010; 184: 236-43.
Stoitzner P, Romani N, McLellan AD, Tripp CH, Ebner S. Isolation of skin dendritic cells from mouse and man. Methods 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-terminus. Hybridoma 2009; 28: 423-9.
McLellan AD. Exosome release by primary B cells. Critical 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 receptor. Journal 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 receptors. Trends 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.
