Actimmune (interferon gamma-1 b) / Clinigen, Amgen - LARVOL DELTA

Reprogramming engineered autologous T cells to overcome resistance in patients with Merkel cell carcinoma. (PubMed, Sci Transl Med) - P1/2 | "Seven patients with ICI-refractory metastatic MCPyV+ MCC received TCRMCC1-transduced cells (TTCR-MCC1 cells) after lymphodepleting chemotherapy or HLA-enhancing interventions [radiation or interferon gamma-1b (Actimmune)], with concurrent ICIs (NCT03747484)...These modifications enhanced tumor infiltration, increased HLA expression, and improved control of HLAlow MCC in vivo in mice. These findings support the feasibility of TCR-engineered cell therapy for MCPyV+ MCC and provide a blueprint for overcoming immune evasion via targeted localized enhancement of antigen presentation."

IO biomarker • Journal • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • CD200R1 • CD28 • CD4 • CD8 • HLA-A

Interferon-? (IFN-?) With Donor Leukocyte Infusion to Treat Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndromes Post Allogeneic Hematopoietic Stem Cell Transplantation (clinicaltrials.gov) - P2 | N=57 | Recruiting | Sponsor: Sawa Ito, MD | Trial completion date: Oct 2027 ➔ Oct 2029 | Trial primary completion date: Oct 2027 ➔ Oct 2029

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • FLT3 • IDH1 • NPM1

Safety and Efficacy of Interferon-Gamma 1b in Patients With Candidemia (clinicaltrials.gov) - P2 | N=65 | Completed | Sponsor: Radboud University Medical Center | Active, not recruiting ➔ Completed | N=200 ➔ 65

Enrollment change • Trial completion

Immune and pharmacodynamic effects of sotorasib plus panitumumab in KRAS G12C-mutant colorectal cancer: Paired biopsy results from CodeBreaK 101 (AACR 2026) - P1 | "Paired biopsy analysis revealed potent MAPK inhibition and immune remodeling, providing mechanistic insight into the role of the immune TME in early response to sotorasib plus panitumumab and underscoring opportunities for rational combination strategies in mCRC."

Biopsy • PK/PD data • Colorectal Cancer • Oncology • Solid Tumor • CD8 • CXCL10 • CXCL9 • CXCR6 • DUSP6 • EPHA4 • ETV4 • HER-2 • HLA-DPA1 • IFNG • KRAS

Non-genetic determinants driving the evolutional trajectories of drug-tolerant-persisters in KRAS Non-small cell lung cancer (AACR 2024) - "In summary, our study unveils the heterogeneity in persister evolution trajectories in KRAS NSCLC. Our platform identifies targetable persister populations in NSCLC models and offers a proof-of-concept for non-standard strategies to combat drug resistance based on persister cell states."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDK4 • FOXP1 • IFNG • IRF1 • KRAS • MCL1 • ZNF384

IFN-γ and donor leukocyte infusion to treat relapsed myeloblastic malignancies after allogeneic hematopoietic stem cell transplantation (AACR 2024) - P1 | "Patients self-administered 100mcg IFN-γ (Actimmune, Horizon Therapeutics) three times a week for 4 weeks (cohort 1) or 1 week (cohort 2), followed by DLI and concurrent IFN-γ for a total of 12 weeks... This first in human use of IFN-γ to treat post-transplant relapse was safe, with a promising efficacy signal when combined with DLI. Correlative studies support our hypothesis that in vivo IFN-γ activates myeloblasts, manifest by HLA-DR upregulation and CIITA induction. We plan to design a phase 2 trial to formally test the efficacy of this novel immunotherapeutic approach to boost GVL in alloSCT."

First-in-human • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CIITA • IFNG

Mapping the hypoxic regulation of IFNγ and TNFα-mediated kinase pathways in melanoma (AACR 2025) - "In the present work we unveil strong diversity on the kinome of melanoma cells when exposed to the inflammatory cytokines IFNγ and TNFα under different oxygen levels. These results provide deeper insight into the mechanisms by which hypoxia contributes to immune evasion and response to cytokines. Our data can help inform future therapeutic strategies targeting these pathways to enhance immune-mediated tumor suppression."

Melanoma • Oncology • Solid Tumor • IFNG • TNFA

Safety and Efficacy of Interferon-Gamma 1b in Patients With Candidemia (clinicaltrials.gov) - P2 | N=200 | Active, not recruiting | Sponsor: Radboud University Medical Center | Recruiting ➔ Active, not recruiting

Enrollment closed

The Battle within: AML´s p53 Strategies to Evade T-Cell Attack (ASH 2023) - "Bispecific T-cell recruiting antibody constructs (BsAb) have shown clinical efficacy with Blinatumomab, a CD3xCD19 BiTE® construct used for the treatment of relapsed or refractory B-cell precursor ALL...Secretome analyses indicated TGF-β as a prominent cytokine leading to an impairment of T-cell function. Further studies are needed to understand the influence of p53 on the TGF-β pathway in AML cells."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology • CD2 • CD33 • IFNG • IL18 • IL2 • TGFB1

Sting Activation Improves T-Cell Engaging Immunotherapy of Acute Myeloid Leukemia (ASH 2023) - "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."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • CXCL10 • CXCL11 • GZMB • IFI16 • IFNA1 • IFNG • IL2 • IRF7 • LAMP1 • RSAD2 • STAT1 • TNFA

Determining Optimal NK Cell Features for Immune Engagement with Tri-specific Killer Engager Molecules (PCF 2025) - "GMP production of camB7-H3 TriKE has been completed by a qualified contractor and clinical stability studies are pending. We anticipate submission of an Investigational New Drug application to the FDA in the 4th quarter of 2025 for consideration of a phase Ia/Ib basket clinical trial with a prostate cancer specific arm and expansion cohort. Anticipated first patient dosing is April 2026."

IO biomarker • Trispecific • Genito-urinary Cancer • Prostate Cancer • Solid Tumor • IFNG • IL15 • IL2RA • IL6 • LAMP1

A high-throughput assay using dysfunctional T cells for phenotypic screening immune checkpoint modulators. (PubMed, J Immunol Methods) - "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."

Journal • Infectious Disease • Oncology • IFNG • IL2

IFN-γand donor leukocyte infusions for relapsed myeloblastic malignancies after allogeneic hematopoietic stem cell transplantation . (PubMed, JCI Insight) - P1 | "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."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • Respiratory Diseases • Transplantation • IFNG

ImmunoSep: Personalized Immunotherapy in Sepsis (clinicaltrials.gov) - P2 | N=280 | Completed | Sponsor: Hellenic Institute for the Study of Sepsis | Active, not recruiting ➔ Completed | Trial completion date: Apr 2025 ➔ Apr 2024

Trial completion • Trial completion date • Infectious Disease • Septic Shock

STING activation improves T-cell-engaging immunotherapy for acute myeloid leukemia. (PubMed, Blood) - "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."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • IFNG • STING • TNFA

Assessing Functional Similarity of Biosimilar ABP 654 and Ustekinumab in Samples from Patients with Crohn's Disease. (PubMed, J Inflamm Res) - "These studies demonstrated similar inhibition of IL-23 and IL-12 function by ABP 654 and ustekinumab RP in both healthy and CD PBMCs. Overall, these assays support the conclusion that ABP 654 and ustekinumab RP are functionally similar, thereby contributing to the TOE supporting a demonstration of biosimilarity."

Journal • Crohn's disease • Gastroenterology • Immunology • Inflammation • Inflammatory Bowel Disease • IFNG • IL12A • IL17A • IL23A • STAT3 • STAT4

Safety and Efficacy of Interferon-Gamma 1b in Patients With Candidemia (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Radboud University Medical Center | Trial completion date: Jun 2027 ➔ Jun 2026 | Trial primary completion date: Jan 2027 ➔ Jun 2026

Trial completion date • Trial primary completion date

ATTAC-MCC: Gene-Modified Immune Cells (FH-MCVA2TCR) in Treating Patients With Metastatic or Unresectable Merkel Cell Cancer (clinicaltrials.gov) - P1/2 | N=7 | Terminated | Sponsor: Fred Hutchinson Cancer Center | Trial completion date: Jan 2025 ➔ Jan 2024 | Active, not recruiting ➔ Terminated; Terminated due to insufficient funding

Immune cell • Metastases • Trial completion date • Trial termination • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Solid Tumor • HLA-A

The battle within: AML´s p53 strategies to evade T-cell attack (SITC 2024) - "Secretome analysis identified TGF-β as a cytokine impairing T-cell function. Ethics Approval Samples from healthy donors and samples from AML patients were collected with written consent in accordance with the Declaration of Helsinki and with approval from the Institutional Review Board of LMU Munich."

IO biomarker • Acute Myelogenous Leukemia • Oncology • IFNG • IL18 • IL2 • TGFB1

Safety and Efficacy of Interferon-Gamma 1b in Patients with Candidemia (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Radboud University Medical Center | Trial completion date: Jan 2025 ➔ Jun 2027 | Trial primary completion date: Jan 2025 ➔ Jan 2027

Trial completion date • Trial primary completion date

Interferon-γ (IFN-γ) With Donor Leukocyte Infusion to Treat Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndromes Post Allogeneic Hematopoietic Stem Cell Transplantation (clinicaltrials.gov) - P2 | N=45 | Recruiting | Sponsor: Sawa Ito, MD | Trial primary completion date: Aug 2026 ➔ Oct 2027

Combination therapy • Trial primary completion date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • IFNG

Looking Past the Interference: Toddler with Persistent Fever, Rash, and Lymphadenopathy (AAP-NCE 2024) - "This case highlights the importance of the timely identification of atypical pathogens, recognition of immunodeficiencies in patients, and connection with sub-specialty services for appropriate highly specialized treatment."

Dermatology • Hematological Disorders • Herpes Simplex • Herpes Zoster • Immunology • Infectious Disease • Nontuberculous Mycobacterial Disease • Pediatrics • Thrombocytosis • Varicella Zoster • IFNGR1

Interferon-γ (IFN-γ) With Donor Leukocyte Infusion to Treat Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndromes Post Allogeneic Hematopoietic Stem Cell Transplantation (clinicaltrials.gov) - P2 | N=45 | Recruiting | Sponsor: Sawa Ito, MD | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • IFNG

Interferon-γ (IFN-γ) With Donor Leukocyte Infusion to Treat Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndromes Post Allogeneic Hematopoietic Stem Cell Transplantation (clinicaltrials.gov) - P2 | N=45 | Not yet recruiting | Sponsor: Sawa Ito, MD

Combination therapy • New P2 trial • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • IFNG

Association of Cytokine Proteins with Disease Activity in Neuromyelitis Optica Spectrum Disorder Participants Receiving Inebilizumab Treatment (AAN 2024) - P2/3 | "Pro-inflammatory cytokines were elevated in a subset of N-MOmentum participants at baseline including IL-6, IL-17a, and IFN inducible chemokines. Longitudinal analysis revealed a correlation with MRI findings over trial of N-MOmentum. Regardless of baseline cytokine levels, improvement in disease activity was observed with inebilizumab treatment."

CNS Disorders • Hematological Disorders • Immunology • Neuromyelitis Optica Spectrum Disorder • Rare Diseases • Rheumatology • CXCL10 • IFNG • IL17A • IL6 • TGFB1