P1, N=12, Recruiting, BlueSky Immunotherapies GmbH

P3, N=142, Active, not recruiting, Biogen | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2024 --> May 2027

P=N/A, N=200, Enrolling by invitation, BlueSky Immunotherapies GmbH | Trial completion date: Oct 2024 --> Jan 2025 | Trial primary completion date: Oct 2024 --> Jan 2025

P=N/A, N=4, Active, not recruiting, Bayer | Not yet recruiting --> Active, not recruiting | N=100 --> 4 | Initiation date: Sep 2024 --> Mar 2024

P2, N=100, Recruiting, Tel-Aviv Sourasky Medical Center

P1/2, N=0, Withdrawn, Fred Hutchinson Cancer Center | N=24 --> 0 | Not yet recruiting --> Withdrawn

P1/2, N=100, Recruiting, T3 Pharmaceuticals AG | Trial completion date: Feb 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Feb 2026

P3, N=142, Recruiting, Biogen | Trial completion date: Nov 2029 --> May 2027 | Trial primary completion date: Nov 2029 --> Jul 2024

P=N/A, N=100, Not yet recruiting, Bayer | Initiation date: May 2024 --> Sep 2024

P1/2, N=24, Not yet recruiting, Fred Hutchinson Cancer Center | Trial completion date: Nov 2026 --> Oct 2027 | Initiation date: May 2024 --> Apr 2025 | Trial primary completion date: Nov 2026 --> Oct 2027

P1/2, N=24, Not yet recruiting, Fred Hutchinson Cancer Center | Initiation date: Dec 2023 --> Mar 2024

STUDY DESIGN AND METHODS Objectives and endpoints: Primary objective: To evaluate the safety and feasibility of FP-1201 in patients undergoing treatment with axi-cel or brexu-cel with two co-primary endpoints: i) to estimate the incidence of dose-limiting toxicity rates within the first 14 days following the last administration of FP-1201; ii) to study the type, frequency, and severity of adverse events according to the NCI CTCAE v5.0 from the first administration of FP-1201 and until day +28 after CAR T-cell infusion Secondary objectives: i) To decrease the incidence and severity of ICANS; ii) to decrease the incidence and severity of CRS; iii) to decrease corticosteroid usage; iv) to evaluate the effect of FP-1201 on anti-tumor efficacy Exploratory objectives: To characterize the in vivo effects of FP-1201 on endothelial function, the systemic cytokine milieu, and CAR T-cell function Key inclusion criteria: Adults ≥18 years of age with Karnofsky performance status ≥60% and B-cell non-Hodgkin lymphoma eligible for treatment with axi-cel or brexu-cel Key exclusion criteria: Known hypersensitivity to IFN-beta or major organ dysfunction FP-1201 administration: The FDA-approved IFN-beta-1a Rebif® will be formulated for IV administration (FP-1201). The aim is to demonstrate safety and efficacy and to investigate the biologic mechanisms of IFN-beta-1a in preventing endothelial dysfunction. Additional preclinical and preliminary clinical data will be presented at the meeting.

P1, N=20, Recruiting, BlueSky Immunotherapies GmbH | Not yet recruiting --> Recruiting | Trial completion date: Jun 2024 --> Nov 2024 | Trial primary completion date: Apr 2024 --> Sep 2024

P1, N=20, Not yet recruiting, BlueSky Immunotherapies GmbH | Initiation date: Apr 2023 --> Aug 2023

P1/2, N=24, Not yet recruiting, Fred Hutchinson Cancer Center

P1, N=20, Not yet recruiting, BlueSky Immunotherapies GmbH

It was also found that FTR33 interacted with melanoma differentiation associated gene 5 (MDA5) or mitochondrial anti-viral signaling protein (MAVS) to weaken the promoter activity of type I IFN. It is thus concluded that the FTR33, as an ISG, in zebrafish can negatively regulate IFN-mediated antiviral response.

Upon secretion, IFNα2b binds to the IFNα receptor on bladder cancer and other cells, resulting in signaling via the JAK-STAT pathway. A plethora of induced IFN-stimulated genes containing IFN-sensitive response elements that contribute to activation of pathways restrict cancer growth.

Our study provides novel insights into the mechanism behind the interferon-mediated upregulation of TRAIL and its protein accumulation in cancer cells. Further investigation is required to understand the role of intracellular TRAIL or depict the mechanisms mediating its apoptosis impairment in cancer cells.

Anakinra (IL-1 inhibitor) and tocilizumab (IL-6 inhibitor) did not mediate any antiviral activity. Our findings indicate that the combined use of IFN-β plus remdesivir or chloroquine induces maximal antiviral activity against human coronavirus strain OC43 in primary human respiratory epithelial cells. Furthermore, our experimental OC43 virus infection model provides an excellent method for evaluating the biological activity of antiviral drugs.

Unique gene expression patterns in patients with IIM with different disease activity levels and MSA types suggest different pathophysiologies. Especially, B cells may contribute to common and MSA-specific immunological pathways in IIM.

This survival gain was no longer detected when the IFNAR1-depleted GL-261 cells were inoculated into IFNAR1-deficient mice. Altogether these data suggest that constitutive type I IFN signaling in gliomas may be pro-tumorigenic, but only in a microenvironment that is proficient for type I IFN signaling in the host.

Here, we demonstrate that phosphoprotein of aMPV subgroup C (aMPV/C) selectively inhibits the nuclear translocation of interferon regulatory 3 (IRF3), instead of affecting the expression and phosphorylation of IRF3, which finally downregulates IFN-I production. This study showed a novel mechanism for aMPV/C infection antagonizing the host IFN response.

The risk of CAN can be evaluated by assessing ADAR1 expression in the rectum of MES0 UC patients, freeing UC patients from unnecessary colonoscopy and reducing their physical burden. RNA editing may be involved in UC carcinogenesis, and may be used to facilitate the prevention and treatment of CAN in UC.

To block type I IFN signaling, the cells were treated with ruxolitinib or MAVS silencing...ERVmap_1248 and LTR7Y can be detected in the PM plasma. We provide clues for patient stratification especially for immunotherapy where best clinical responses are associated with an activated basal immune response.

In support of these results, targeting MUC1-C in wild-type BRCA TNBC cells enhanced carboplatin-induced DNA damage and the loss of self-renewal capacity. In addition, MUC1-C was necessary for DNA damage resistance, self-renewal, and tumorigenicity in olaparib-resistant BRCA1-mutant TNBC cells...These findings demonstrate that MUC1-C activates PBRM1, and thereby chromatin remodeling of IFN-stimulated genes that promote chronic inflammation, DNA damage resistance, and immune evasion. Implications: MUC1-C is necessary for PBRM1-driven chromatin remodeling in chronic activation of IFN pathway genes that promote DNA damage resistance and immunosuppression.

Poly (I:C)-treated Pim1 mice produced less serum IFN-β and were less likely to survive than wild-type mice. These findings show for the first time that Pim1 participates in TLR-mediated IFN-β production, thus revealing a novel target for controlling antiviral innate immune responses.

We found that high basal levels of SOCS1 inhibit STAT1 activation and subsequently IFN-induced UBE2L6 and ISGylation in iPSCs. Importantly, epigenetic regulation of SOCS1 and subsequently ISGylation may be important factors in the development of cell type-specific host defense responses in hepatocytes that should be considered when studying chronic infections and oncogenic processes in the liver.

Furthermore, inhibition of JAK signaling with tofacitinib reduced cytokine production and ameliorated mucosal damage, enabling the survival of poly(I:C)-injected hM-R822Q Tg mice. These findings demonstrate that the MDA5 R822Q mutant introduces a critical risk factor for uncontrollable inflammation on viral infection or vaccination.

TLR9-increased expression was associated with HPV persistence in previous studies; hence, bacterial coinfections may enhance this risk. Prospective measurements of type III IFNs and IFNLR1 are warranted to evaluate whether this response may act as a double-edged sword in infected epithelia.

Inhibition of JAK/STAT/BST2 axis attenuated CD40-induced antiviral effect. In conclusion, a functional variant of CD40 modulates HBV clearance via regulation of the ANXA2/CD40/BST2 axis, which may shed new light on HBV personalized therapy.

Zoledronic acid (Zol) is a potent bisphosphonate that inhibits the differentiation of monocytes into osteoclasts. Altogether, our findings suggest Zol+Dex block the differentiation of osteoclasts through the expression of IFN-β. Revealing the molecular pathway behind this regulation may lead to the development of IFN-β-based therapy to inhibit osteoclastogenesis in multiple myeloma patients.

Moreover, the mechanisms underlying IFN activity are discussed, which indicated its potential as a novel treatment for CHB. It is proposed that epigenetic changes such as histone acetylation, DNA methylation, m6A methylation could be the targets of IFN, which may offer a novel approach to HBV treatment.

We utilized scRNA sequencing to characterize the peripheral immune response to PD-1 blockade and more broadly define non-CD8+ dependent mechanisms of immune evasion in cHL.Peripheral blood mononuclear cells were obtained from 20 patients with relapsed/refractory (R/R) cHL treated with PD-1 blockade (nivolumab) on the CheckMate 205 clinical trial (cycle 1 day 1 [C1D1] and cycle 4 day 1 [C4D1]) 11 patients with newly diagnosed previously untreated cHL and 13 healthy donors.Unlike healthy donors all evaluated patients with cHL had circulating IFN stimulated adaptive and innate populations including several distinct CD4+ T-cell effectors and an NK cell subset with reduced cytotoxic potential and decreased numbers of B cells at all stages of differentiation...Monocytes from patients whose disease progressed following PD-1 blockade expressed significantly higher levels of immunosuppressive cytokine/chemokine signature which led to the development of a predictive transcriptional assay. We identified a comparable circulating monocyte population and transcriptional signature associated with unresponsiveness to PD-1 blockade in an additional solid tumor underscoring the broad-based significance of these findings.

Our results suggest that loss of Hsd17b13 protects mice from NASH fibrosis through augmentation of hepatocyte IFN signaling, with IFNs as plausible mediators to mitigate HSC activation. These findings shed new lights on novel strategies to treat NASH-related fibrosis.

CLL cells were found to make low amounts of IFN via TANK-binding kinase 1 pathways, but p-STAT1 and -STAT2 proteins along with IFN-stimulated genes that reflect IFN activation were variably downregulated in cultured CLL cells by the neutralizing IFNAR1 Ab anifrolumab...Autocrine IFN protected responsive CLL cells from stressful tissue culture environments and therapeutic drugs such as ibrutinib and venetoclax in vitro, in part by upregulating Mcl-1 expression. These findings suggest hypersensitivity to IFN may promote aggressive clinical behavior. Specific blockade of IFN signaling may improve outcomes for patients with CLL with higher-risk disease.

Furthermore, inhibition of JAK signaling with tofacitinib reduced cytokine production and ameliorated mucosal damage, enabling the survival of poly(I:C)-injected hM-R822Q Tg mice. These findings demonstrate that the MDA5 R822Q mutant introduces a critical risk factor for uncontrollable inflammation on viral infection or vaccination.

We also showed that inhibition of STAT3 activation reduced SOCS3 levels, while the presence of the estrogen-ERαp66 signaling pathway stabilized SOCS3 levels. The results from this study will aid our understanding of the mechanism of HEV pathogenesis and immune response during pregnancy.