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Review

TIM-3 pathway dysregulation and targeting in cancer

, &
Pages 523-534 | Received 13 Oct 2020, Accepted 15 Dec 2020, Published online: 19 Jan 2021

References

  • Vinay DS, Ryan EP, Pawelec G, et al. Immune evasion in cancer: mechanistic basis and therapeutic strategies. Semin Cancer Biol. 2015;35(suppl):S185–S198. .
  • Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–264.
  • Riva A, Chokshi S. Immune checkpoint receptors: homeostatic regulators of immunity. Hepatol Int. 2018;12(3):223–236.
  • Darvin P, Toor SM, Sasidharan Nair V, et al. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med. 2018;50:1–11.
  • Havel JJ, Chowell D, Chan TA. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat Rev Cancer. 2019;19:133–150.
  • Dyck L, Mills KHG. Immune checkpoints and their inhibition in cancer and infectious diseases. Eur J Immunol. 2017;47:765–779.
  • Khan M, Lin J, Liao G, et al. Comparative analysis of immune checkpoint inhibitors and chemotherapy in the treatment of advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2018;97(33):e11936.
  • Chen R, Hou X, Yang L, et al. Comparative efficacy and safety of first-line treatments for advanced non-small cell lung cancer with immune checkpoint inhibitors: a systematic review and meta-analysis. Thorac Cancer. 2019;10(4):607–623.
  • Pons-Tostivint E, Latouche A, Valflard P, et al. Comparative analysis of durable responses on immune checkpoint inhibitors versus other systemic therapies: a pooled analysis of phase III trials. In: JCO Precis Oncol. Alexandria, VA, USA: American Society of Clinical Oncology; 2019. p. 3.
  • Sharma P, Hu-Lieskovan S, Wargo JA, et al. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell. 2017;168(4):707–723.
  • Dong S, Ghobrial IM. Immunotherapy for hematological malignancies. J Life Sci. Westlake Village. 2019;1:46–52.
  • Ok CY, Young KH. Checkpoint inhibitors in hematological malignancies. J Hematol Oncol. 2017;10:103.
  • JP B, Stahl M, AM Z. Immune checkpoint-based therapy in myeloid malignancies: a promise yet to be fulfilled. Expert Rev Anticancer Ther. 2019;19::393–404.
  • Burugu S, Dancsok AR, Nielsen TO. Emerging targets in cancer immunotherapy. Semin Cancer Biol. 2018;52:39–52.
  • Gupta S, Thornley TB, Gao W, et al. Allograft rejection is restrained by short-lived TIM-3+PD-1+Foxp3+ Tregs. J Clin Invest. 2012;122:2395–2404.
  • Sakuishi K, Ngiow SF, Sullivan JM, et al. TIM3+FOXP3+ regulatory T cells are tissue-specific promoters of T-cell dysfunction in cancer. Oncoimmunology. 2013;2:e23849.
  • Chiba S, Baghdadi M, Akiba H, et al. Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol. 2012;13:832–842.
  • Ndhlovu LC, Lopez-Vergès S, Barbour JD, et al. Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity. Blood. 2012;119:3734–3743.
  • Khademi M, Illes Z, Gielen AW, et al. T Cell Ig- and mucin-domain-containing molecule-3 (TIM-3) and TIM-1 molecules are differentially expressed on human Th1 and Th2 cells and in cerebrospinal fluid-derived mononuclear cells in multiple sclerosis. J Immunol. 2004;172:7169–7176.
  • Das M, Zhu C, Kuchroo VK. Tim-3 and its role in regulating anti-tumor immunity. Immunol Rev. 2017;276(1):97–111.
  • Kikushige Y, Shima T, Takayanagi S, et al. TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells. Cell Stem Cell. 2010;7(6):708–717. .
  • Sakuishi K, Apetoh L, Sullivan JM, et al. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med. 2010;207(10):2187–2194.
  • Gao X, Zhu Y, Li G, et al. TIM-3 expression characterizes regulatory T cells in tumor tissues and is associated with lung cancer progression. PLoS One. 2012;7(2):e30676.
  • Zhang Y, Cai P, Liang T, et al. TIM-3 is a potential prognostic marker for patients with solid tumors: A systematic review and meta-analysis. Oncotarget. 2017;8(19):31705–31713.
  • Jiang J, Jin MS, Kong F, et al. Decreased galectin-9 and increased Tim-3 expression are related to poor prognosis in gastric cancer. PLoS One. 2013;8:e81799.
  • Granier C, Dariane C, Combe P, et al. Tim-3 Expression on Tumor-Infiltrating PD-1 + CD8 + T Cells correlates with poor clinical outcome in renal cell carcinoma. Cancer Res. 2017;77(5):1075–1082.
  • Jenkins RW, Barbie DA, Flaherty KT. Mechanisms of resistance to immune checkpoint inhibitors. Br J Cancer. 2018;118:9–16.
  • Freeman GJ, Casasnovas JM, Umetsu DT, et al. TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity. Immunol Rev. 2010;235(1):172–189.
  • Monney L, Sabatos CA, Gaglia JL, et al. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature. 2002;415(6871):536–541.
  • Cao E, Zang X, Ramagopal UA, et al. T cell immunoglobulin mucin-3 crystal structure reveals a galectin-9-independent ligand-binding surface. Immunity. 2007;26(3):311–321.
  • Kundapura SV, Ramagopal UA. The CC’ loop of IgV domains of the immune checkpoint receptors, plays a key role in receptor: ligand affinity modulation. Sci Rep. 2019;9:19191.
  • Lee J, Su EW, Zhu C, et al. Phosphotyrosine-dependent coupling of Tim-3 to T-cell receptor signaling pathways. Mol Cell Biol. 2011;31(19):3963–3974.
  • Geng H, Zhang GM, Li D, et al. Soluble form of T cell Ig mucin 3 is an inhibitory molecule in T cell-mediated immune response. J Immunol. 2006;176:1411–1420.
  • Rangachari M, Zhu C, Sakuishi K, et al. Bat3 promotes T cell responses and autoimmunity by repressing Tim-3-mediated cell death and exhaustion. Nat Med. 2012;18:1394–1400.
  • Clayton KL, Haaland MS, Douglas-Vail MB, et al. T cell Ig and mucin domain-containing protein 3 is recruited to the immune synapse, disrupts stable synapse formation, and associates with receptor phosphatases. J Immunol. 2014;192:782–791.
  • Anderson AC, Joller N, Kuchroo VK. Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity. 2016;44(5):989–1004.
  • van de Weyer PS, Muehlfeit M, Klose C, et al. A highly conserved tyrosine of Tim-3 is phosphorylated upon stimulation by its ligand galectin-9. Biochem Biophys Res Commun. 2006;351(2):571–576.
  • Huang YH, Zhu C, Kondo Y, et al. CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature. 2015;517:386–390.
  • Kikushige Y, Miyamoto T, Yuda J, et al. A TIM-3/Gal-9 autocrine stimulatory loop drives self-renewal of human myeloid leukemia stem cells and leukemic progression. Cell Stem Cell. 2015;17(3):341–352.
  • DeKruyff RH, Bu X, Ballesteros A, et al. T cell/transmembrane, Ig, and mucin-3 allelic variants differentially recognize phosphatidylserine and mediate phagocytosis of apoptotic cells. J Immunol. 2010;184(4):1918–1930.
  • Zhu C, Anderson AC, Schubart A, et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005;6(12):1245–1252.
  • Wang Y, Zhao E, Zhang Z, et al. Association between Tim3 and Gal9 expression and gastric cancer prognosis. Oncol Rep. 2018;40:2115–2126.
  • Gonçalves Silva I, Yasinska IM, Sakhnevych SS, et al. The Tim-3-galectin-9 secretory pathway is involved in the immune escape of human acute myeloid leukemia cells. EBioMedicine. 2017;22:44–57.
  • Li H, Wu K, Tao K, et al. Tim-3/galectin-9 signaling pathway mediates T-cell dysfunction and predicts poor prognosis in patients with hepatitis B virus-associated hepatocellular carcinoma. Hepatology. 2012;56(4):1342–1351.
  • Yasinska IM, Sakhnevych SS, Pavlova L, et al. The Tim-3-galectin-9 pathway and its regulatory mechanisms in human breast cancer. Front Immunol. 2019;10:1594.
  • Kang CW, Dutta A, Chang LY, et al. Apoptosis of tumor infiltrating effector TIM-3+CD8+ T cells in colon cancer. Sci Rep. 2015;5:15659.
  • Kammerer R, Stober D, Singer BB, et al. Carcinoembryonic antigen-related cell adhesion molecule 1 on murine dendritic cells is a potent regulator of T cell stimulation. J Immunol. 2001;166(11):6537–6544.
  • Horst AK, Bickert T, Brewig N, et al. CEACAM1+ myeloid cells control angiogenesis in inflammation. Blood. 2009;113(26):6726–6736.
  • Wiener Z, Kohalmi B, Pocza P, et al. TIM-3 is expressed in melanoma cells and is upregulated in TGF-beta stimulated mast cells. J Invest Dermatol. 2007;127:906–914.
  • Coutelier J-P, Godfraind C, Dveksler GS, et al. B lymphocyte and macrophage expression of carcinoembryonic antigen-related adhesion molecules that serve as receptors for murine coronavirus. Eur J Immunol. 1994;24(6):1383–1390.
  • Gebauer F, Wicklein D, Horst J, et al. Carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1, 5 and 6 as biomarkers in pancreatic cancer. PLoS One. 2014;9(11):e113023.
  • Zhang Y, Cai P, Li L, et al. Co-expression of TIM-3 and CEACAM1 promotes T cell exhaustion in colorectal cancer patients. Int Immunopharmacol. 2017;43:210–218.
  • Sabatos-Peyton CA, Nevin J, Brock A, et al. Blockade of Tim-3 binding to phosphatidylserine and CEACAM1 is a shared feature of anti-TIM-3 antibodies that have functional efficacy. Oncoimmunology. 2018;7:e1385690.
  • Fadok VA, Voelker DR, Campbell PA, et al. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol. 1992;148:2207–2216.
  • Nakayama M, Akiba H, Takeda K, et al. Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation. Blood. 2009;113(16):3821–3830.
  • Ocana-Guzman R, Torre-Bouscoulet L, Sada-Ovalle ITIM-3. regulates distinct functions in macrophages. Front Immunol. 2016;7:229.
  • Jan M, Chao MP, Cha AC, et al. Prospective separation of normal and leukemic stem cells based on differential expression of TIM3, a human acute myeloid leukemia stem cell marker. Proc Natl Acad Sci U S A. 2011;108(12):5009–5014.
  • Tang D, Lotze MT. Tumor immunity times out: TIM-3 and HMGB1. Nat Immunol. 2012;13(9):808–810.
  • Andersson U, Ottestad W, Tracey KJ. Extracellular HMGB1: a therapeutic target in severe pulmonary inflammation including COVID-19? Mol Med. 2020;26(1):42.
  • Curtin JF, Liu N, Candolfi M, et al. HMGB1 mediates endogenous TLR2 activation and brain tumor regression. PLoS Med. 2009;6(1):e10.
  • Yang ZZ, Grote DM, Ziesmer SC, et al. IL-12 upregulates TIM-3 expression and induces T cell exhaustion in patients with follicular B cell non-Hodgkin lymphoma. J Clin Invest. 2012;122:1271–1282.
  • Zhou Q, Munger ME, Veenstra RG, et al. Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia. Blood. 2011;117(17):4501–4510.
  • Wang Z, Zhu J, Gu H, et al. The clinical significance of abnormal Tim-3 expression on NK cells from patients with gastric cancer. Immunol Invest. 2015;44(6):578–589.
  • Yu M, Lu B, Liu Y, et al. Tim-3 is upregulated in human colorectal carcinoma and associated with tumor progression. Mol Med Rep. 2017;15:689–695.
  • da Silva IP, Gallois A, Jimenez-Baranda S, et al. Reversal of NK-cell exhaustion in advanced melanoma by Tim-3 blockade. Cancer Immunol Res. 2014;2:410–422.
  • Sabatos CA, Chakravarti S, Cha E, et al. Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance. Nat Immunol. 2003;4(11):1102–1110.
  • Jones RB, Ndhlovu LC, Barbour JD, et al. Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection. J Exp Med. 2008;205(12):2763–2779.
  • Fourcade J, Sun Z, Benallaoua M, et al. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients. J Exp Med. 2010;207:2175–2186.
  • Liu J, Zhang S, Hu Y, et al. Targeting PD-1 and Tim-3 pathways to reverse CD8 T-cell exhaustion and enhance ex vivo T-cell responses to autologous dendritic/tumor vaccines. J Immunother. 2016;39:171–180.
  • Koyama S, Akbay EA, Li YY, et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. 2016;7(1):10501.
  • Lu X, Yang L, Yao D, et al. Tumor antigen-specific CD8+ T cells are negatively regulated by PD-1 and Tim-3 in human gastric cancer. Cell Immunol. 2017;313:43–51.
  • Gautron AS, Dominguez-Villar M, de Marcken M, et al. Enhanced suppressor function of TIM-3+ FoxP3+ regulatory T cells. Eur J Immunol. 2014;44:2703–2711.
  • Yan J, Zhang Y, Zhang JP, et al. Tim-3 expression defines regulatory T cells in human tumors. PLoS One. 2013;8:e58006.
  • Liu JF, Wu L, Yang LL, et al. Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer. J Exp Clin Cancer Res. 2018;37:44.
  • Schieber M, Crispino JD, Stein B. Myelofibrosis in 2019: moving beyond JAK2 inhibition. Blood Cancer J. 2019;9:74.
  • Liu Y, Bewersdorf JP, Stahl M, et al. Immunotherapy in acute myeloid leukemia and myelodysplastic syndromes: the dawn of a new era? Blood Rev. 2019;34:67–83.
  • Agrawal V, Gbolahan OB, Stahl M, et al. Vaccine and cell-based therapeutic approaches in acute myeloid leukemia. Curr Cancer Drug Targets. 2020;20(7):473–489.
  • Boddu P, Kantarjian H, Garcia-Manero G, et al. The emerging role of immune checkpoint based approaches in AML and MDS. Leuk Lymphoma. 2018;59(4):790–802.
  • Lamble AJ, Lind EF. Targeting the immune microenvironment in acute myeloid leukemia: a focus on T cell immunity. Front Oncol. 2018;8:213.
  • Lamble AJ, Kosaka Y, Laderas T, et al. Reversible suppression of T cell function in the bone marrow microenvironment of acute myeloid leukemia. Proc Natl Acad Sci U S A. 2020 Jun;23(117):14331–14341.
  • Veletic I, Prijic S, Manshouri T, et al. Altered T-cell subset repertoire affects treatment outcome of patients with myelofibrosis. Haematologica. 2020. DOI:10.3324/haematol.2020.249441.
  • Zeidan AM, Knaus HA, Robinson TM, et al. A multi-center phase I trial of ipilimumab in patients with myelodysplastic syndromes following hypomethylating agent failure. Clin Cancer Res. 2018;24(15):3519–3527.
  • Wendelbo O, Nesthus I, Sjo M, et al. Functional characterization of T lymphocytes derived from patients with acute myelogenous leukemia and chemotherapy-induced leukopenia. Cancer Immunol Immunother. 2004;53:740–747.
  • Garcia-Manero G, Sasaki K, Montalban-Bravo G, et al. A phase II study of nivolumab or ipilimumab with or without azacitidine for patients with myelodysplastic syndrome (MDS). Blood. 2018;132. abstract 465
  • Garcia-Manero G, Tallman MS, Martinelli G, et al. Pembrolizumab, a PD-1 inhibitor, in patients with myelodysplastic syndrome (MDS) after failure of hypomethylating agent treatment. Blood. 2016;128. DOI:10.1182/blood.V128.22.345.345. abstract 345
  • Davids MS, Kim HT, Bachireddy P, et al. Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med. 2016;375(2):143–153.
  • Daver N, Boddu P, Garcia-Manero G, et al. Hypomethylating agents in combination with immune checkpoint inhibitors in acute myeloid leukemia and myelodysplastic syndromes. Leukemia. 2018;32(5):1094–1105.
  • Khaznadar Z, Henry G, Setterblad N, et al. Acute myeloid leukemia impairs natural killer cells through the formation of a deficient cytotoxic immunological synapse. Eur J Immunol. 2014;44(10):3068–3080.
  • Zeidan AM, Cavenagh J, Voso MT, et al. Efficacy and safety of azacitidine (AZA) in combination with the anti-PD-L1 durvalumab (durva) for the front-line treatment of older patients (pts) with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy (IC) and pts with higher-risk myelodysplastic syndromes (HR-MDS): results from a large, international, randomized phase 2 study. Blood. 2019;134. abstract 829
  • Zhou M, Sacirbegovic F, Zhao K, et al. T cell exhaustion and a failure in antigen presentation drive resistance to the graft-versus-leukemia effect. Nat Commun. 2020;11(1):4227.
  • Krejcik J. van de Donk N. Trogocytosis represents a novel mechanism of action of daratumumab in multiple myeloma. Oncotarget. 2018;9:33621–33622.
  • Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–447.
  • Vandsemb EN, Kim TK, Zeidan AM. Will deeper characterization of the landscape of immune checkpoint molecules in acute myeloid leukemia bone marrow lead to improved therapeutic targeting? Cancer. 2019;125(9):1410–1413.
  • Bewersdorf JP, Shallis RM, Zeidan AM. Immune checkpoint inhibition in myeloid malignancies: moving beyond the PD-1/PD-L1 and CTLA-4 pathways. In: Blood Rev. Amsterdam, the Netherland: Elsevier; 2020. p. 100709.
  • Kikushige Y, Miyamoto T. Identification of TIM-3 as a leukemic stem cell surface molecule in primary acute myeloid leukemia. Oncology. 2015;89(suppl 1):28–32.
  • Kikushige Y, Miyamoto T. TIM-3 as a novel therapeutic target for eradicating acute myelogenous leukemia stem cells. Int J Hematol. 2013;98(6):627–633.
  • Asayama T, Tamura H, Ishibashi M, et al. Functional expression of Tim-3 on blasts and clinical impact of its ligand galectin-9 in myelodysplastic syndromes. Oncotarget. 2017;8(51):88904–88917.
  • Dama P, Tang M, Fulton N, et al. Gal9/Tim-3 expression level is higher in AML patients who fail chemotherapy. J Immunother Cancer. 2019;7:175.
  • Kong Y, Zhang J, Claxton DF, et al. PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation. Blood Cancer J. 2015;5:e330.
  • Gonçalves Silva I, Rüegg L, Gibbs BF, et al. The immune receptor Tim-3 acts as a trafficker in a Tim-3/galectin-9 autocrine loop in human myeloid leukemia cells. Oncoimmunology. 2016;5(7):e1195535.
  • Dardalhon V, Anderson AC, Karman J, et al. Tim-3/Galectin-9 Pathway: regulation of Th1 Immunity through Promotion of CD11b + Ly-6G + Myeloid Cells. J Immunol. 2010;185(3):1383–1392.
  • Williams P, Basu S, Garcia-Manero G, et al. The distribution of T-cell subsets and the expression of immune checkpoint receptors and ligands in patients with newly diagnosed and relapsed acute myeloid leukemia. Cancer. 2019;125:1470–1481.
  • Ogata K, Kakumoto K, Matsuda A, et al. Differences in blast immunophenotypes among disease types in myelodysplastic syndromes: a multicenter validation study. Leuk Res. 2012 Oct;36(10):1229–1236.
  • Zhou Q, Munger ME, Highfill SL, et al. Program death-1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia. Blood. 2010;116:2484–2493.
  • Wolff F, Leisch M, Greil R, et al. The double-edged sword of (re)expression of genes by hypomethylating agents: from viral mimicry to exploitation as priming agents for targeted immune checkpoint modulation. Cell Commun Signal. 2017;15(1):13.
  • Liu L, Chang YJ, Xu LP, et al. T cell exhaustion characterized by compromised MHC class I and II restricted cytotoxic activity associates with acute B lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation. Clin Immunol. 2018;190:32–40.
  • Blaeschke F, Willier S, Stenger D, et al. Leukemia-induced dysfunctional TIM-3+CD4+ bone marrow T cells increase risk of relapse in pediatric B-precursor ALL patients. Leukemia. 2020;34(10):2607–2620.
  • Rezazadeh H, Astaneh M, Tehrani M, et al. Blockade of PD-1 and TIM-3 immune checkpoints fails to restore the function of exhausted CD8+ T cells in early clinical stages of chronic lymphocytic leukemia. Immunol Res. 2020;68(5):269–279.
  • Murga-Zamalloa CA, Brown NA, Wilcox RA. Expression of the checkpoint receptors LAG-3, TIM-3 and VISTA in peripheral T cell lymphomas. J Clin Pathol. 2020;73(4):197–203.
  • Laken H, McEachern K, Murtaza A, et al. Discovery of TSR-022, a novel, potent anti-TIM-3 therapeutic antibody. Eur J Cancer. 2016;69. DOI:10.1016/S0959-8049(16)32902-1. abstract S2102
  • Weiss GJ, Luke JL, Falchook G, et al. A phase 1 study of TSR-022, an anti-TIM-3 monoclonal antibody, in patients (pts) with advanced solid tumors. J Immunother Cancer. 2017;5. abstract O13
  • Davar D, Boasberg P, Eroglu Z, et al. A phase 1 study of TSR-022, an anti-TIM-3 monoclonal antibody, in combination with TSR-042 (anti-PD-1) in patients with colorectal cancer and post-PD-1 NSCLC and melanoma. J Immunother Cancer. 2018;6. DOI:10.1186/s40425-018-0393-z. abstract O42
  • Harding JJ, Patnaik A, Moreno V, et al. A phase Ia/Ib study of an anti-TIM-3 antibody (LY3321367) monotherapy or in combination with an anti-PD-L1 antibody (LY3300054): interim safety, efficacy, and pharmacokinetic findings in advanced cancers. J Clin Oncol. abstract 12. 2019;37(suppl 8). DOI:10.1200/JCO.2019.37.8_suppl.12
  • Sabatos-Peyton CA MBG453: a high affinity, ligand-blocking anti-TIM-3 monoclonal Ab. Presented at: 107th AACR Annual Meeting; April 16-20, 2016; New Orleans, LA.
  • Curigliano G, Gelderblom H, Mach N, et al. Phase (Ph) I/II study of MBG453 ± spartalizumab (PDR001) in patients (pts) with advanced malignancies. Cancer Res. 2019;79:13suppl; abstract CT18
  • Borate U, Esteve J, Porkka K, et al. Anti-TIM-3 antibody MBG453 in combination with hypomethylating agents in patients with high-risk myelodysplastic syndrome and acute myeloid leukemia: a phase 1 study. Paper presented at: 25th EHA Congress; June 11-21, 2020 [ abstract S185].
  • Brunner A, Narayan R, Esteve J, et al. Post-transplant outcomes of patients with MDS and AML after receiving hypomethylating agent therapy combined with the TIM-3 inhibitor, MBG453. Poster presented at 25th EHA Congress; June 11-21, 2020 [ abstract EP828].
  • Zeidan AM, Kim HJ, Miyazaki Y, et al. The STIMULUS clinical trial program: evaluating combination therapy with sabatolimab in patients with higher-risk myelodysplastic syndrome (HR-MDS) or acute myeloid leukemia (AML). Poster presented at 8th SOHO Annual Meeting; 2020 September 9-12 [ poster AML-187].
  • Martins F, Sykiotis GP, Maillard M, et al. New therapeutic perspectives to manage refractory immune checkpoint-related toxicities. Lancet Oncol. 2019;20(1):e54–e64.
  • He X, Feng Z, Ma J, et al. Bispecific and split CAR T cells targeting CD13 and TIM3 eradicate acute myeloid leukemia. Blood. 2020;135(10):713–723.