Actimmune (interferon gamma-1 b)

Cell lysates in the same assay plate were used for a viability assay to assess cytotoxicity. This workflow was implemented for assessing 15 compounds selected based on cellular pathways they modulate, of which 2 compounds promoted IL-2 and IFN-γ production in dysfunctional T cells upon activation, suggesting potential therapeutic values against T cell dysfunction.

IFN-γ was safe and well tolerated in this phase I study of IFN-γ for relapsed AML/MDS post-alloSCT, with a promising efficacy signal when combined with DLI. Larger studies are needed to formally test the efficacy of this approach.TRIAL RESGISTRATION.

We established a key role for IFNγ in AMG 330-mediated cytotoxicity against AML cells, and in rendering AML cells responsive to STING agonism. Here, we propose to improve the efficacy of CD33-targeting BsAbs by combining them with a STING agonist.

P2, N=200, Recruiting, Radboud University Medical Center | Trial completion date: Jun 2027 --> Jun 2026 | Trial primary completion date: Jan 2027 --> Jun 2026

P2, N=200, Recruiting, Radboud University Medical Center | Trial completion date: Jan 2025 --> Jun 2027 | Trial primary completion date: Jan 2025 --> Jan 2027

P2, N=45, Recruiting, Sawa Ito, MD | Trial primary completion date: Aug 2026 --> Oct 2027

P1/2, N=7, Terminated, Fred Hutchinson Cancer Center | Trial completion date: Jan 2025 --> Jan 2024 | Active, not recruiting --> Terminated; Terminated due to insufficient funding

P2, N=45, Recruiting, Sawa Ito, MD | Not yet recruiting --> Recruiting

P2, N=45, Not yet recruiting, Sawa Ito, MD

P1/2, N=7, Active, not recruiting, Fred Hutchinson Cancer Center | Recruiting --> Active, not recruiting | N=16 --> 7 | Trial completion date: Apr 2025 --> Jan 2025 | Trial primary completion date: Apr 2024 --> Jan 2024

P1, N=8, Completed, Sawa Ito, MD | Recruiting --> Completed

We propose a novel mechanism by which AMG 330-activated T cells prime and sensitize AML target cells in a forward feedback loop towards STING activation, leading to increased type-I-IFN production and induction of ISGs. The beneficial effect of physiological cGAMP in enhancing AMG 330-mediated cytotoxicity was accompanied by the pronounced expression of effector cytokines and an overall cytotoxic T-cell phenotype. We established a key role for interferon gamma in AMG 330-mediated cytotoxicity of AML cells and in rendering AML cells responsive to STING agonism.