Leader, Cancer Immunology, Inflammation and Tolerance Program
GRU Cancer Center
Bradley-Turner & GRA Eminent Scholar in Molecular Immunogenetics
Professor of Medicine
1120 15th Street, CN 4151
Phone: (706) 721-8735
Dr. Mellor is the co-leader of the Cancer Immunology, Inflammation and Tolerance program in the GRU Cancer Center. He was the founding director of the MCG Immunotherapy Center from 2002 until 2012 and holds the Bradley-Turner/Georgia Research Alliance Eminent Scholar Chair in Molecular Immunogenetics. He is a professor in the Department of Medicine at the Medical College of Georgia and in the College of Graduate Studies at Georgia Health Sciences University. Dr. Mellor received his BA and MA from the University of Cambridge, UK and earned his PhD from the University of London in 1979 for his thesis work at the Imperial Cancer Research Fund.
Dr. Mellor’s research focuses on the role of tissue inflammation and the immune system in disease processes. His primary research goals are to elucidate fundamental inflammatory processes that impact immune responses and cause diseases such as cancer and autoimmune and infectious diseases, and to develop novel therapies for such diseases by identifying new molecular and cellular targets for intervention.
Dr. Mellor’s laboratory studies the role of the immune regulatory enzyme indoleamine 2,3 dioxygenase (IDO) in controlling responses by T cells, which mediate cellular immunity and facilitate humoral (antibody-mediated) immunity. Local IDO is associated with many malignancies from the earliest stages of tumor progression. IDO is also associated with persistent infections for which no effective vaccines exist, such as HIV-1, the virus that causes AIDS. In autoimmune syndromes IDO impedes immune-mediated destruction of healthy tissues by mediating local tryptophan catabolism and causing metabolic changes that attenuate natural and artificial (vaccine-induced) immunity. Tumors exploit this tissue protective property of IDO to suppress local anti-tumor immunity. Consequently, IDO is a major barrier to clinical success after cancer immunotherapy, even when cancer vaccines or immunomodulators show immunologic efficacy. This insight suggests that IDO inhibitor drugs will enhance vaccine efficacy.
Conversely, reagents that stimulate IDO may be effective in protecting healthy tissues at risk from destruction by immunity that develops in patients with autoimmune syndromes and after life-saving organ and tissue transplants. To this end, Dr. Mellor’s group is studying DNA nanoparticles that stimulate IDO to alleviate immune-mediated tissue injury in mouse models of Type I insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and multiple sclerosis (MS). This research facilitates understanding how tumor-associated IDO protects developing malignancies (in the pre-clinical period) from natural anti-tumor immunity, and how IDO impedes efforts to eradicate tumors after clinical presentation using standard (chemo, radio) therapies, and novel immunotherapies.
Research in Dr. Mellor’s laboratory has generated substantial intellectual property in various stages of development from early disclosure to patent awards, and licensing to corporate partners. One corporate partner is promoting Phase II clinical trials with an IDO inhibitor to determine if this compound is efficacious in promoting cancer immunotherapy in combination with current standards of clinical care and novel immunotherapies.
- National Institute Of Allergy And Infectious Diseases: “Manipulating natural host immunoregulation via IDO during viral infection” 2009-2014, A. Mellor, PI
- National Institute Of Allergy And Infectious Diseases: “T cell regulation by IDO-competent plasmacytoid dendritic cells” 2009-2011, A. Mellor, PI
- National Institute Of Allergy And Infectious Diseases: “IDO-dependent T cell suppression” 2004-2010, A. Mellor, PI
- Carlos and Marguerite Mason Trust: “Innovative approaches to prolong transplant survival, and reduce the fiscal and health burden of long term drug therapy to transplant patients” 2009-2011
- Juvenile Diabetes Research Foundation:“Creating local suppressive inflammation to block Type 1 diabetes progression” 2008-2011
Grant information is updated quarterly.
Makala LH, Baban B, Lemos H, El-Awady AR, Chandler PR, Hou DY, Munn DH, Mellor AL. Leishmania major Attenuates Host Immunity by Stimulating Local Indoleamine 2,3-Dioxygenase Expression. J Infect Dis. 2011 Mar;203(5):715-25.
Sharma MD, Hou DY, Baban B, Koni PA, He Y, Chandler PR, Blazar BR, Mellor AL, Munn DH. Reprogrammed foxp3(+) regulatory T cells provide essential help to support cross-presentation and CD8(+) T cell priming in naive mice. Immunity. 2010 Dec 14;33(6):942-54.
Zhou Q, Xiao H, Liu Y, Peng Y, Hong Y, Yagita H, Chandler P, Munn DH, Mellor A, Fu N, He Y. Blockade of programmed death-1 pathway rescues the effector function of tumor-infiltrating T cells and enhances the antitumor efficacy of lentivector immunization. J Immunol. 2010 Nov 1;185(9):5082-92.
Johnson BA 3rd, Kahler DJ, Baban B, Chandler PR, Kang B, Shimoda M, Koni PA, Pihkala J, Vilagos B, Busslinger M, Munn DH, Mellor AL. B-lymphoid cells with attributes of dendritic cells regulate T cells via indoleamine 2,3-dioxygenase. Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10644-8.
Huang L, Baban B, Johnson BA 3rd, Mellor AL. Dendritic cells, indoleamine 2,3 dioxygenase and acquired immune privilege. Int Rev Immunol. 2010 Apr;29(2):133-55. Review.
Wang Y, Liu H, McKenzie G, Witting PK, Stasch JP, Hahn M, Changsirivathanathamrong D, Wu BJ, Ball HJ, Thomas SR, Kapoor V, Celermajer DS, Mellor AL, Keaney JF Jr, Hunt NH, Stocker R. Kynurenine is an endothelium-derived relaxing factor produced during inflammation. Nat Med. 2010 Mar;16(3):279-85.
Johnson BA 3rd, Baban B, Mellor AL. Targeting the immunoregulatory indoleamine 2,3 dioxygenase pathway in immunotherapy. Immunotherapy. 2009 Jul;1(4):645-61.
Ding ZC, Blazar BR, Mellor AL, Munn DH, Zhou G. Chemotherapy rescues tumor-driven aberrant CD4+ T-cell differentiation and restores an activated polyfunctional helper phenotype.Blood. 2010 Mar 25;115(12):2397-406.
Singh N, Yamamoto M, Takami M, Seki Y, Takezaki M, Mellor AL, Iwashima M. CD4(+)CD25(+) regulatory T cells resist a novel form of CD28- and Fas-dependent p53-induced T cell apoptosis. J Immunol. 2010 Jan 1;184(1):94-104.
Jasperson LK, Bucher C, Panoskaltsis-Mortari A, Mellor AL, Munn DH, Blazar BR. Inducing the tryptophan catabolic pathway, indoleamine 2,3-dioxygenase (IDO), for suppression of graft-versus-host disease (GVHD) lethality. Blood. 2009 Dec 3;114(24):5062-70.
Baban B, Chandler PR, Sharma MD, Pihkala J, Koni PA, Munn DH, Mellor AL. IDO activates regulatory T cells and blocks their conversion into Th17-like T cells. J Immunol. 2009 Aug 15;183(4):2475-83.
Cobbold SP, Adams E, Farquhar CA, Nolan KF, Howie D, Lui KO, Fairchild PJ, Mellor AL, Ron D, Waldmann H. Infectious tolerance via the consumption of essential amino acids and mTOR signaling. Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12055-60.
Sharma MD, Hou DY, Liu Y, Koni PA, Metz R, Chandler P, Mellor AL, He Y, Munn DH. Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood. 2009 Jun 11;113(24):6102-11.
Kim YH, Choi BK, Kang WJ, Kim KH, Kang SW, Mellor AL, Munn DH, Kwon BS. IFN-gamma-indoleamine-2,3 dioxygenase acts as a major suppressive factor in 4-1BB-mediated immune suppression in vivo. J Leukoc Biol. 2009 May;85(5):817-25.
Colvin BL, Sumpter TL, Tokita D, Salati J, Mellor AL, Thomson AW. Allostimulatory activity of bone marrow-derived plasmacytoid dendritic cells is independent of indoleamine dioxygenase but regulated by inducible costimulator ligand expression. Hum Immunol. 2009 May;70(5):313-20.
Kahler DJ, Mellor AL. T cell regulatory plasmacytoid dendritic cells expressing indoleamine 2,3 dioxygenase. Handb Exp Pharmacol. 2009;(188):165-96. Review.
Miu J, Ball HJ, Mellor AL, Hunt NH. Effect of indoleamine dioxygenase-1 deficiency and kynurenine pathway inhibition on murine cerebral malaria. Int J Parasitol. 2009 Feb;39(3):363-70.
Muller AJ, Sharma MD, Chandler PR, Everhart ME, Johnson BA, Kahler DJ, Pihkala J, DuHadaway J, Munn DH, Prendergast G, Mellor AL. Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2,3 dioxygenase. Proc. Natl. Acad. Sci. 2008;105:17073-78.
Mohib K, Wang S, Guan Q, Mellor AL, Sun H, Du C, Jevnikar AM. Indoleamine 2,3-dioxygenase expression promotes renal ischemia-reperfusion injury.Am J Physiol Renal Physiol. 2008 Jul;295(1):F226-34.
Xu H, Oriss TB, Fei M, Henry AC, Melgert BN, Chen L, Mellor AL, Munn DH, Irvin CG, Ray P, Ray A. Indoleamine 2,3-dioxygenase in lung dendritic cells promotes Th2 responses and allergic inflammation. Proc Natl Acad Sci USA. 2008 May 6;105(18):6690-5.
Harrington L, Srikanth CV, Antony R, Rhee SJ, Mellor AL, Shi HN, Cherayil BJ. Deficiency of indoleamine 2,3-dioxygenase enhances commensal-induced antibody responses and protects against Citrobacter rodentium-induced colitis. Infect Immun. 2008 Jul;76(7):3045-53.
Jasperson LK, Bucher C, Panoskaltsis-Mortari A, Taylor PA, Mellor AL, Munn DH, Blazar BR. Indoleamine 2,3- dioxygenase is a critical regulator of acute graft-versus-host disease lethality. Blood. 2008 Mar 15;111(6):3257-65.
Mellor AL, Munn DH. Creating immune privilege: active local suppression that benefits friends, but protects foes. Nat Rev Immunol. 2008 Jan;8(1):74-80. Review. Erratum in: Nat Rev Immunol. 2008 Feb;8(2):160.
Banerjee T, DuHadaway JB, Gaspari P, Sutanto-Ward E, Munn DH, Mellor AL , Malachowski WP, Prendergast GC, Muller AJ. A key in vivo antitumor mechanism of action of natural product-based brassinin is inhibition of indoleamine 2,3-dioxygenase. Oncogene. 2008 May 1;27(20):2851-7.
Publications are updated quarterly. For a complete listing, see Dr. Mellor’s work on PubMed.
Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B, Brown C, Mellor AL. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 1998;281:1122-4.
Mellor AL, Sivakumar J, Chandler P, Smith K, Molina H, Mao D, Munn DH. Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nature Immunology 2001;2:64-8.
Munn DH, Sharma MD, Lee JR, Jhaver KG, Johnson TS, Keskin DB, Marshall B, Chandler P, Antonia SJ, Burgess R, Slingluff CL Jr, Mellor AL. Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 2002;297:1867-70.
Mellor AL, Baban B, Chandler P, Marshall B, Jhaver K, Hansen A, Koni PA, Iwashima M, Munn DH. Cutting edge: induced indoleamine 2,3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion. J Immunol 2003;171(4):1652-5.
Mellor AL, Chandler PR, Baban B, Hansen AM, Marshall B, Pihkala J, Waldmann H, Cobbold SP, Adams E, Munn DH. Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2,3 dioxygenase. Int Immunol 2004;16(10):1391-1401.
Mellor AL, Baban B, Chandler PR, Manlapat A, Kahler DJ, Munn DH. Cutting Edge: CpG Oligonucleotides Induce Splenic CD19+ Dendritic Cells to Acquire Potent Indoleamine 2,3-Dioxygenase-Dependent T Cell Regulatory Functions via IFN Type 1 Signaling. J Immunol 2005;175(9):5601-5.
Baban B, Hansen AM, Chandler PR, Manlapat A, Bingaman A, Kahler DJ, Munn DH, Mellor AL. A minor population of splenic dendritic cells expressing CD19 mediates IDO-dependent T cell suppression via type I IFN signaling following B7 ligation. Int Immunol 2005;17:909-9.
Munn DH, Sharma MD, Hou D, Baban B, Lee J, Antonia SJ, Messina JL, Chandler P, Koni PA, Mellor AL. Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J Clin Invest 2004;114(4):280-90.
Munn DH, Sharma MD, Baban B, Harding HP, Zhang Y, Ron D, Mellor AL. GCN2 Kinase in T Cells Mediates Proliferative Arrest and Anergy Induction in Response to Indoleamine 2,3-Dioxygenase. Immunity 2005;22(5):633-42.
Sharma MD, Baban B, Chandler PR, Hou DY, Singh N, Yagita H, Azuma M, Blazar BR, Mellor AL, Munn DH. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes activate mature Tregs via indoleamine 2,3-dioxygenase. J Clin Invest 2007;117(9):2570–82.
Mellor AL, Munn DH. Creating immune privilege: active local suppression that benefits friends, but protects foes. Nat Rev Immunol 2008;8(1):74-80. Erratum in: Nat Rev Immunol 2008;8(2):160.
Mellor AL, Munn DH. Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? Immunol Today 1999;20(10):469-73.
Muller AJ, Sharma MD, Chandler PR, DuHadaway JB, Everhart ME, Johnson BA, Kahler DJ, Pihkala J, Soler AP, Munn DH, Prendergast GC, Mellor AL. Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2,3 dioxygenase. Proc Natl Acad Sci USA. 2008 Nov 4;104:17073-17078.
- Professor, Medical College of Georgia, Cellular Biology and Anatomy, College of Graduate Studies, Georgia Health Sciences University; Georgia Research Alliance Eminent Scholar in Immunogenetics
- Associate director, Institute of Molecular Medicine and Genetics
- Member, British Society for Immunology
- Member, American Association for the Advancement of Science
- Member, American Association of Immunologists