OX40 Agonism

OX40 is a co-stimulatory receptor expressed on activated CD4+ and CD8+ T cells that:

  • Prolongs CD4+ and CD8+ T-cell survival and memory generation1,2

  • Prevents T-cell tolerance1

  • Reduces the immunosuppressive activity of regulatory T cells1,3

Activation of OX40 can also be achieved through the use of agonistic OX40-directed antibodies.4 Such treatment has the potential to enhance T-cell stimulation and promote potential tumor killing by the immune system. Agonistic OX40-directed antibodies can work as monotherapy or in combination with other immunotherapies to augment antitumor immune responses.1

Video: “Activating the OX40/OX40 L axis”Video: “Activating the OX40/OX40 L axis”
OX40 agonism MOA pt.1 OX40 agonism MOA pt.2
OX40 agonism MOA pt.1 OX40 agonism MOA pt.2

MHC: major histocompatibility complex; TCR: T-cell receptor

MEDI0562

An OX40 agonist compound is currently in clinical development to determine its antitumor effect because it may enhance T-cell stimulation and promote tumor killing by the immune system4,5:

  • MEDI0562 (humanized OX40 mAb)

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STAT3 Inhibition

STAT3 (signal transducer and activator of transcription 3) is a transcription factor that plays a critical role in normal cell proliferation, differentiation, and apoptosis (programmed cell death).6,7 Constitutive activation of STAT3 has been identified in many types of tumors.6-8

AZD9150 is an investigational, generation 2.5 antisense oligonucleotide that prevents STAT3 expression, thereby blocking tumor-intrinsic and tumor-extrinsic STAT3-mediated signaling.5

STAT3 inhibition

STAT3: signal transducer and activator of transcription 3; GF: growth factor; SRC: Src kinase; JAK: janus kinase; ABL: abelson tyrosine kinase; ISRE: interferon-sensitive response element

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STAT3 Inhibition

STAT3 (signal transducer and activator of transcription 3) is a transcription factor that plays a critical role in normal cell proliferation, differentiation, and apoptosis (programmed cell death).6,7 Constitutive activation of STAT3 has been identified in many types of tumors.6-8

Reveal more about STAT3 inhibition

AZD9150 is an investigational, generation 2.5 antisense oligonucleotide that prevents STAT3 expression, thereby blocking tumor-intrinsic and tumor-extrinsic STAT3-mediated signaling.5

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STAT3 inhibition

STAT3: signal transducer and activator of transcription 3; GF: growth factor; SRC: Src kinase; JAK: janus kinase; ABL: abelson tyrosine kinase; ISRE: interferon-sensitive response element

Explore our Clinical Trial Development Program

PD-1 Inhibition

PD-1 (programmed cell death 1) is a cell surface receptor that interacts with 2 ligands, PD-L1 and PD-L2 (programmed cell death ligand-1,-2), to deliver inhibitory signals to T cells, limiting their function.9,10

Blockade of PD-1 or modulation of PD-1 expression thus increases T-cell function and can potentiate antitumor immunity.9

MEDI0680 is an investigational anti-PD-1 monoclonal antibody (mAb) that is currently being evaluated for safety and efficacy in human clinical trials.5

PD-1 inhibition and T cell activation pt.1 PD-1 inhibition and T cell activation pt.2
PD-1 inhibition and T cell activation pt.1 PD-1 inhibition and T cell activation pt.2

PD-1: programmed cell death-1; PD-L1: programmed cell death ligand-1; PD-L2: programmed cell death ligand-2; MHC: major histocompatibility complex; TCR: T-cell receptor

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References: 1. Gao J, Bematchez C, Sharma P, et al. Advances in the development of cancer immunotherapies. Trends lmmunol. 2013:34(2):90-98. 2. Jensen SM, Maston LD, Gough MJ, et al. Signaling through OX40 enhances antitumor immunity. Semin Oncol. 2010:3(5)7:524-532. 3. Vu MD, Xiao X, Gao W, et al. OX40 costimulation turns off Foxp3+ Tregs. Blood. 2007;110(10):2501-2510. 4. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011:480(7378):480-489. 5. AstraZeneca. Clinical Trials Appendix Full-Year and Q4 2016 Update. 21 February 2017. 6. Bar-Natan M, Nelson EA, Xiang M, Frank DA. STAT signaling in the pathogenesis and treatment of myeloid malignancies. JAKSTAT. 2012:(2)1:55-64. 7. Qi QR, Yang ZM. Regulation and function of signal transducer and activator of transcription. World J Biol Chem. 2014;5(2):231-239. 8. Walker SR, Frank DA. Screening approaches to generating STAT inhibitors: Allowing the hits to identify the targets. JAKSTAT. 2012:1(4):292-299. 9. Sznol M. Chen L. Antagonist antibodies to PD-1 and 87-Hl (PO·Ll) in the treatment of human cancer. Clin Cancer Res. 2013:19(5):1021-1034. 10. Creelan BC. Update on immune checkpoint inhibitors in lung cancer. Cancer Control. 2014:21:80-89.