Telratolimod (MEDI 9197)

Telratolimod is an agonist of toll-like receptor 7 (TLR7) and TLR8.¹ It increases the production of IL-8 in HEK293 cells expressing human TLR7 or TLR8 and increases protein levels of IFN-α and TNF-α in isolated human peripheral blood mononuclear cells (PBMCs). Telratolimod (1 mg/kg) increases the HA-induced secretion of IFN-γ in mouse splenocytes ex vivo but does not induce the production of TNF-α in mouse serum in vivo. Telratolimod nanoparticles, when used as an adjuvant with the HIV-1 envelope glycoprotein, enhance neutralizing antibody responses to an HIV-1 pseudovirus in rhesus macaques for at least one year.² Intratumoral administration of telratolimod reduces tumor growth and increases metastasis-free survival in E0771 and 4T1.2 murine mammary carcinoma models and increases intratumoral production of cytokines in a 4T1.2 murine model, an effect that is enhanced by coadministration of anti-PD-1 antibodies.³

1.Smirnov, D., Schmidt, J.J., Capecchi, J.T., et al.Vaccine adjuvant activity of 3M-052: An imidazoquinoline designed for local activity without systemic cytokine inductionVaccine29(33)5434-5442(2011) 2.Kasturi, S.P., Rasheed, M.A.U., Havenar-Doughton, C., et al.3M-052, a synthetic TLR-7/8 agonist, induces durable HIV-1 envelope–specific plasma cells and humoral immunity in nonhuman primatesSci. Immunol.5(48)eabb1025(2020) 3.Zanker, D.J., Spurling, A.J., Brockwell, N.K., et al.Intratumoral administration of the Toll-like receptor 7/8 agonist 3M-052 enhances interferon-driven tumor immunogenicity and suppresses metastatic spread in preclinical triple-negative breast cancerClin. Transl. Immunology9(9)e1177(2020)