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    DRUG CLASS:

    IL-27 inhibitor

    Related drugs:
    10d
    A Trial of Casdozokitug in Combination With Toripalimab Plus Bevacizumab in Participants With Unresectable and/or Locally Advanced or Metastatic Hepatocellular Carcinoma (clinicaltrials.gov)
    P2, N=72, Not yet recruiting, Coherus Biosciences, Inc.
    New P2 trial • Combination therapy • Metastases
    |
    Avastin (bevacizumab) • Loqtorzi (toripalimab-tpzi) • casdozokitug (CHS-388)
    2ms
    Prevention of Prostate Cancer Metastasis by a CRISPR-delivering Nanoplatform for Interleukin-30 Genome Editing. (PubMed, Mol Ther)
    PC-Lung and PC-BM 2-OCs revealed that Cas9hIL30-PSCA-NPs suppressed PC cell release of CXCL2/GROβ, which in vivo was associated with intra-metastatic myeloid cell infiltrates, and of DKK1, OPG and IL6, which in vitro boosted endothelial-network formation and cancer cell migration. Development of a patient-tailored nanoplatform for selective CRISPR-mediated IL30 gene deletion is a clinically valuable tool against PC progression.
    Journal
    |
    CXCR4 (Chemokine (C-X-C motif) receptor 4) • IL6 (Interleukin 6) • CDH1 (Cadherin 1) • DKK1 (dickkopf WNT signaling pathway inhibitor 1) • IGF1 (Insulin-like growth factor 1) • MMP2 (Matrix metallopeptidase 2) • CXCR2 (Chemokine (C-X-C motif) receptor 2) • L1CAM (L1 cell adhesion molecule) • TNFSF10 (TNF Superfamily Member 10) • PSCA (Prostate Stem Cell Antigen 2)
    2ms
    Immunoliposome-based targeted delivery of the CRISPR/Cas9gRNA-IL30 complex inhibits prostate cancer and prolongs survival. (PubMed, Exp Mol Med)
    In the syngeneic PC model, IL30-targeting immunoliposomes downregulated NFKB1 expression and prevented intratumoral influx of CD11b+Gr-1+MDCs, Foxp3+Tregs, and NKp46+RORγt+ILC3, and prolonged host survival by inhibiting tumor progression. This study serves as a proof of principle that immunoliposome-based targeted delivery of Cas9gRNA-IL30 represent a potentially safe and effective strategy for PC treatment.
    Journal • IO biomarker
    |
    PTEN (Phosphatase and tensin homolog) • HGF (Hepatocyte growth factor) • CDH1 (Cadherin 1) • EFNB2 (Ephrin B2) • VEGFD (Vascular Endothelial Growth Factor D) • CCL2 (Chemokine (C-C motif) ligand 2) • ITGAM (Integrin, alpha M) • TGFB1 (Transforming Growth Factor Beta 1) • FOXP3 (Forkhead Box P3) • SERPINE1 (Serpin Family E Member 1) • DKK3 (Dickkopf WNT Signaling Pathway Inhibitor 3) • IL1B (Interleukin 1, beta) • CXCL1 (Chemokine (C-X-C motif) ligand 1) • PSCA (Prostate Stem Cell Antigen 2)
    |
    PTEN expression • CDH1 expression • NFKB1 expression • HGF expression • FOXP3 expression
    4ms
    Role of IL-27 in COVID-19: A Thin Line between Protection and Disease Promotion. (PubMed, Int J Mol Sci)
    Regardless of the pathological process it is involved in, IL-27 is critical for upholding the necessary balance between tissue damage and cytotoxicity against infectious agents and/or tumors. In COVID-19, it is involved in multiple processes, including antiviral cytotoxicity via CD8+ cells, IgG subclass switching, and even the activation of Tregs.
    Review • Journal
    |
    CD8 (cluster of differentiation 8)
    4ms
    Intraperitoneal activation of myeloid cells clears ascites and reveals IL27-dependent regression of metastatic ovarian cancer. (PubMed, bioRxiv)
    Finally, BI extended mouse survival in a chemoresistant model and significantly improved chemotherapy response in a chemo-sensitive model. In summary, we propose a new therapeutic strategy for the treatment of metastatic OvCa.
    Journal • Metastases
    |
    IFNG (Interferon, gamma) • SYK (Spleen tyrosine kinase) • CLEC7A (C-Type Lectin Domain Containing 7A)
    6ms
    Trial of Atezolizumab and Bevacizumab With SRF388 or Placebo in Patients With Hepatocellular Carcinoma (clinicaltrials.gov)
    P2, N=134, Active, not recruiting, Coherus Biosciences, Inc. | Trial completion date: Mar 2025 --> May 2026 | Trial primary completion date: Mar 2024 --> May 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • casdozokitug (CHS-388)
    6ms
    IL-27 maintains cytotoxic Ly6C+ γδ T cells that arise from immature precursors. (PubMed, EMBO J)
    We show that IL-27 supports the cytotoxic phenotype and function of mouse CD27+Ly6C+ cells and human Vδ2+ cells, while IL-27 is dispensable for mouse CD27+Ly6C- cell and human Vδ1+ cell functions. These data reveal increased complexity within IFNγ-producing γδ-T cells, comprising immature and terminally differentiated subsets, that offer new insights into unconventional T-cell biology.
    Journal • IO biomarker
    |
    IFNG (Interferon, gamma) • CD27 (CD27 Molecule)
    9ms
    Trial of Atezolizumab and Bevacizumab With SRF388 or Placebo in Patients With Hepatocellular Carcinoma (clinicaltrials.gov)
    P2, N=134, Active, not recruiting, Coherus Biosciences, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • casdozokitug (CHS-388)
    10ms
    Deletion of IL-27p28 induces CD8 T cell immunity against colorectal tumorigenesis. (PubMed, Int Immunopharmacol)
    Our results suggest that loss of IL-27p28 suppresses colorectal tumorigenesis by augmenting CD8 T cell-mediated anti-tumor immunity. Targeting IL-27p28 could be developed as a novel strategy for the treatment of colorectal cancers.
    Journal
    |
    CD8 (cluster of differentiation 8)
    11ms
    KEYNOTE-C16: Study of CHS-388 (Formerly Know as SRF388) in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=260, Recruiting, Coherus Biosciences, Inc. | Trial completion date: May 2024 --> Aug 2026 | Trial primary completion date: May 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    Keytruda (pembrolizumab) • Loqtorzi (toripalimab-tpzi) • casdozokitug (CHS-388)
    11ms
    Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units. (PubMed, Open Med (Wars))
    The sST2, cannot predict death in critically-ill patients as a single prognostic factor. However, the combination of at least two biomarkers: IL-33, sST2, IL-27, and galectin-3, gives very significant results in predicting the outcome in patients admitted to ICUs.
    Journal
    |
    IL33 (Interleukin 33) • ST2 (Suppression Of Tumorigenicity)
    11ms
    Interleukin-30 subverts prostate cancer-endothelium crosstalk by fostering angiogenesis and activating immunoregulatory and oncogenic signaling pathways. (PubMed, J Exp Clin Cancer Res)
    IL30 regulates the crosstalk between PC and EC and reshapes their transcriptional profiles, triggering angiogenic, immunoregulatory and oncogenic gene expression programs. These findings highlight the angiostatic and oncostatic efficacy of targeting IL30 to fight PC.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • PD-1 (Programmed cell death 1) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • STAT3 (Signal Transducer And Activator Of Transcription 3) • IDO1 (Indoleamine 2,3-dioxygenase 1) • FASLG (Fas ligand) • IGF1 (Insulin-like growth factor 1) • IL10 (Interleukin 10) • CCR7 (Chemokine (C-C motif) receptor 7) • CCND2 (Cyclin D2) • IL17A (Interleukin 17A) • STAT6 (Signal transducer and activator of transcription 6) • CCR2 (C-C Motif Chemokine Receptor 2) • CXCR5 (C-X-C Motif Chemokine Receptor 5) • IL13 (Interleukin 13) • LGALS4 (Galectin 4) • NOS2 (Nitric Oxide Synthase 2) • TNFSF10 (TNF Superfamily Member 10) • HSPD1 (Heat Shock Protein Family D (Hsp60) Member 1) • JUN (Jun proto-oncogene) • KLK3 (Kallikrein-related peptidase 3) • PTGS1 (Prostaglandin-Endoperoxide Synthase 1)
    |
    TP53 deletion
    12ms
    Results from a phase 2 study of triplet blockade of the IL-27, PD-(L)1, and VEGF pathways with casdozokitug (casdozo, SRF388) in combination with atezolizumab (atezo) and bevacizumab (bev) in patients with unresectable, locally advanced, or metastatic hepatocellular carcinoma (uHCC). (ASCO-GI 2024)
    Clinical Trial Registration Number NCT05359861 Sponsored by Surface Oncology Background: Casdozo is the first in class and only clinical-stage IL-27 targeting antibody, which neutralizes IL-27 in the tumor microenvironment and stimulates antitumor response. Triplet blockade of the IL-27, VEGF, and PD-(L)1 pathways with casdozo/atezo/bev has an acceptable safety profile to date with promising antitumor activity in uHCC that warrants continued exploration. Toxicity was consistent with the known profiles of the agents, with no new safety signals identified. Biomarker analysis to evaluate immune response and associations of IL-27 pathway and clinical outcomes is ongoing.
    Clinical • P2 data • Combination therapy • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    IFNG (Interferon, gamma)
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • Loqtorzi (toripalimab-tpzi) • casdozokitug (CHS-388)
    12ms
    IL-27-induced, MSC-derived Exosomes Promote MMP3 Expression Through the miR-206/L3MBTL4 Axis in Synovial Fibroblasts. (PubMed, Altern Ther Health Med)
    IL-27 can induce the expression of miR-206 in MSCs, and miR-206 can be transported into FLS through MSC-EVs to promote FLS migration and MMP3 expression and aggravate articular cartilage damage. Patients with RA who have a high IL-27 expression may not be suitable to receive treatment with MSCs, and clinicians can use MSCs that knock down or delete IL-27R to treat RA patients who have a high IL-27 expression.
    Journal
    |
    MIR206 (MicroRNA 206) • MMP3 (Matrix metallopeptidase 3)
    over1year
    Constitutive expression of interleukin-27 diminishes proinflammatory cytokine production without impairing effector function of engineered T cells. (PubMed, Cytotherapy)
    We discovered that T cells bearing scIL-27 sustained anti-tumor immunity and cytotoxicity yet manifested a profound reduction in pro-inflammatory cytokines granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha. IL-27-expressing T cells therefore present a potential avenue to avert treatment-related toxicities commonly associated with engineered T-cell therapy due to the reduced pro-inflammatory cytokine profile.
    Journal
    |
    TNFA (Tumor Necrosis Factor-Alpha) • IL27 (Interleukin 27)
    |
    IL2 expression
    over1year
    Interleukin-27 potentiates CD8+ T-cell-mediated anti-tumor immunity in chronic lymphocytic leukemia. (PubMed, Haematologica)
    Finally, we detected a decrease in IL-27 serum levels during CLL development in both pre-clinical and patient samples. Altogether, we demonstrated that IL-27 has a strong antitumorigenic role in CLL and postulate this cytokine as a promising treatment or adjuvant for this malignancy.
    Journal
    |
    CD8 (cluster of differentiation 8)
    over1year
    Detection of sFas, sCD137, and IL-27 Cytokines as Potential Biomarkers for Hepatocellular Carcinoma Diagnosis. (PubMed, J Hepatocell Carcinoma)
    This model has a bias-corrected area under the receiver operating characteristic (ROC) curve (AUC) of 0.948, a sensitivity of 92.11%, a specificity of 93.33%, and an accuracy of 0.925. Our findings suggest that serum cytokines have the potential to be utilized in HCC screening to improve detection rates.
    Journal
    |
    TNFA (Tumor Necrosis Factor-Alpha) • CCL4 (Chemokine (C-C motif) ligand 4)
    over1year
    IFN-β activates cytotoxic function of human natural killer cells toward IL-27 and poly(I:C) stimulated PC3 and DU145 cells. (PubMed, Cell Immunol)
    We further demonstrated that these NK cells killed PC3 cells in a partially TRAIL-dependent manner. This work provides mechanistic insight into how the cytotoxic function of NK cells can be improved to target cancer cells.
    Journal • IO biomarker
    |
    GZMB (Granzyme B) • IFNB1 (Interferon Beta 1)
    over1year
    IL-27 promotes pathogenic Tfh-like CD4 effectors and exhausted-like CD8 T cells in a mouse model of Sjögren’s (P907) (IMMUNOLOGY 2023)
    Through phenotyping these populations, I found IL-27 signaling induced Tfh-like PD-1+ICOS+ CD4 effector T cells and PD-1+ICOS+CD39+ exhausted-like CD8 T cells in the glands of recipient mice. Taken together, these data demonstrate a role for IL-27 in promoting pathogenic T cells in the immune dysregulation of Sjögren’s.
    Preclinical
    |
    CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule) • ICOS (Inducible T Cell Costimulator) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
    over1year
    Structural insights into the assembly of gp130 family cytokine signaling complexes. (PubMed, Sci Adv)
    The acute bends at both signaling receptors in all complexes bring the membrane-proximal domains to a ~30 angstrom range but with distinct distances and orientations. We also reveal how CLCF1 engages its secretion chaperone cytokine receptor-like factor 1. Our data provide valuable insights for therapeutically targeting gp130-mediated signaling.
    Journal
    |
    IL6 (Interleukin 6)
    over1year
    Inactivation of interleukin-30 in colon cancer stem cells via CRISPR/Cas9 genome editing inhibits their oncogenicity and improves host survival. (PubMed, J Immunother Cancer)
    IL30 is a new CRC driver, since its inactivation, which disables oncogenic pathways and multiple autocrine loops, inhibits CR-CSC tumorigenicity and metastatic ability. The development of CRISPR/Cas9-mediated targeting of IL30 could improve the current therapeutic landscape of CRC.
    Journal • Cancer stem
    |
    CXCR4 (Chemokine (C-X-C motif) receptor 4) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • STAT3 (Signal Transducer And Activator Of Transcription 3) • IGF1 (Insulin-like growth factor 1) • MMP2 (Matrix metallopeptidase 2) • CCR7 (Chemokine (C-C motif) receptor 7) • EGF (Epidermal growth factor)
    over1year
    Cytokine receptor IL27RA is an NF-kB-responsive gene involved in CD38 upregulation in multiple myeloma. (PubMed, Blood Adv)
    In accordance, a subset of MM cell lines and primary MM cells cultured with IL-27 upregulated CD38 cell-surface expression, a finding with potential implications for enhancing the efficacy of CD38-directed monoclonal antibody (mAb) therapies by increasing CD38-expression on tumour cells. The elevated expression of IL-27Rα and JAM2 on MM cells compared to normal PCs may be exploited for the development of targeted therapeutic strategies that modulate the interaction of MM cells with the TME.
    Journal • IO biomarker
    |
    CD38 (CD38 Molecule) • STAT3 (Signal Transducer And Activator Of Transcription 3) • NFKB1 (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) • STAT1 (Signal Transducer And Activator Of Transcription 1) • IL21 (Interleukin 21) • RELA (RELA Proto-Oncogene)
    |
    CD38 expression
    almost2years
    Transcriptomic and Functional Evidence That miRNA193a-3p Inhibits Lymphatic Endothelial Cell (LEC) and LEC + MCF-7 Spheroid Growth Directly and by Altering MCF-7 Secretome. (PubMed, Cells)
    Moreover, miR193a-3p alters factors in MCF-7 secretome, which represses ERK1/2 and Akt phosphorylation, induces pro-apoptotic protein and apoptosis in LECs, and downregulates interferon-associated proteins known to promote cancer growth and metastasis. In conclusion, miR193a-3p can potentially modify the tumor microenvironment by altering pro-growth BC secretome and inhibiting LEC growth, and may represent a therapeutic molecule to target breast tumors/cancer.
    Journal • PARP Biomarker
    |
    ER (Estrogen receptor) • IFNG (Interferon, gamma) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • FASLG (Fas ligand) • HLA-B (Major Histocompatibility Complex, Class I, B) • IFIT1 (Interferon Induced Protein With Tetratricopeptide Repeats 1) • IL1A (Interleukin 1, alpha) • IL32 (Interleukin 32) • IL1R1 (Interleukin 1 receptor, type I) • CRP (C-reactive protein) • IL33 (Interleukin 33) • MIR193A (MicroRNA 193a) • PSMB8 (Proteasome 20S Subunit Beta 8)
    almost2years
    Ten interleukins and risk of prostate cancer. (PubMed, Front Oncol)
    Reverse MR analysis did not find the associations between genetic liability to prostate cancer and higher levels of IL-1ra (β, -0.005; 95% CI, -0.010, 0.001; P=0.111) and IL-6 (β, 0.002; 95% CI, -0.011, 0.014; P=0.755). This MR study suggests that long-term IL-6 may increase the risk of prostate cancer and IL-1ra may reduce it.
    Journal
    |
    CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL18 (Interleukin 18) • IL17A (Interleukin 17A) • IL6R (Interleukin 6 receptor) • IL1R1 (Interleukin 1 receptor, type I) • IL16 (Interleukin 16)
    almost2years
    Identification of a tumor immune-inflammation signature predicting prognosis and immune status in breast cancer. (PubMed, Front Oncol)
    Furthermore, IL27 treatment improved breast cancer cell migration. The TIIS represents a promising prognostic tool for estimating OS in patients with breast cancer and is correlated with immune status.
    Journal • BRCA Biomarker • IO biomarker
    |
    BRCA (Breast cancer early onset) • IL27 (Interleukin 27)
    almost2years
    Novel immune-related prognostic model and nomogram for breast cancer based on ssGSEA. (PubMed, Front Genet)
    The nomogram's 1-, 3-, and 5-year AUCs were .828, .783, and .751, respectively. Overall, our study developed an immune-related model and a nomogram that could reliably predict OS for breast cancer patients, and offered insights into tumor immune and pathological mechanisms.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • NFKBIE (NFKB Inhibitor Epsilon) • CXCL1 (Chemokine (C-X-C motif) ligand 1) • PSMB8 (Proteasome 20S Subunit Beta 8) • RAC2 (Rac Family Small GTPase 2) • SOCS3 (Suppressor Of Cytokine Signaling 3) • ULBP2 (UL16 Binding Protein 2)
    almost2years
    Berberine promotes immunological outcomes and decreases neuroinflammation in the experimental model of multiple sclerosis through the expansion of Treg and Th2 cells. (PubMed, Immun Inflamm Dis)
    Berberine appears to have a protective effect on disease development and alleviating disease status in EAE, which appears to be due to the cell expansion and function of Treg and Th2 cells in addition to berberine's anti-inflammatory properties.
    Journal
    |
    IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • IL10 (Interleukin 10) • TGFB1 (Transforming Growth Factor Beta 1) • IL4 (Interleukin 4) • IL33 (Interleukin 33)
    almost2years
    Lacticaseibacillus rhamnosus Probio-M9-Driven Mouse Mammary Tumor-Inhibitory Effect Is Accompanied by Modulation of Host Gut Microbiota, Immunity, and Serum Metabolome. (PubMed, Nutrients)
    These changes might be associated with the protective effect of Probio-M9 against mammary tumor growth. Thus, probiotic administration could harness host gut microbiome in anti-cancer responses.
    Preclinical • Journal
    |
    IFNG (Interferon, gamma) • IL13 (Interleukin 13) • IL5 (Interleukin 5)
    almost2years
    Immune Profile of Blood, Tissue and Peritoneal Fluid: A Comparative Study in High Grade Serous Epithelial Ovarian Cancer Patients at Interval Debulking Surgery. (PubMed, Vaccines (Basel))
    A differential cytokine profile was found in serum and PF as IL-2, IL-8, IL-15, IL-27, IFN-γ, and GM-CSF were elevated specifically in PF. In conclusion, the differential immune profile and correlation of soluble parameters and NK cell receptors with chemo response score may add knowledge to understand anti-tumor immune response to develop effective treatment modality.
    Journal • Surgery
    |
    IFNG (Interferon, gamma) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL2 (Interleukin 2) • CSF2 (Colony stimulating factor 2) • NCR3LG1 (Natural Killer Cell Cytotoxicity Receptor 3 Ligand 1) • IL15 (Interleukin 15) • NKG2D (killer cell lectin like receptor K1)
    almost2years
    Human Papillomavirus E1 Protein Regulates Gene Expression in Cells Involved in Immune Response. (PubMed, Appl Biochem Biotechnol)
    The mRNA expression was significantly decreased (P < 0.05), and the mRNA expression of IL-27 was significantly increased (P < 0.001), which did not affect the mRNA expression of lymphocyte proliferation and activation-related regulators. The tumor suppressor breast cancer 1 (BRCA1) and antimicrobial peptide CAMP were significantly increased, and decreased (P < 0.001), and the expression of pro-apoptotic factor Caspase9 showed a significant downward trend (P < 0.05).
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • TNFA (Tumor Necrosis Factor-Alpha) • IL10 (Interleukin 10)
    2years
    Immune marker expression of irradiated mesothelioma cell lines. (PubMed, Front Oncol)
    At this timepoint, increases in levels of cytokines IFN-β, MCP-1 and IL-6 were observed following irradiation with 8 Gy in AB1 but not AE17, reflecting patterns in marker expression. Overall, this study establishes the dose- and time-dependent changes in immune marker expression of commonly studied mesothelioma cell lines following radiation and will inform future study into optimal dosing and scheduling of combined radiotherapy and immune checkpoint inhibition for mesothelioma.
    Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL10 (Interleukin 10) • IL17A (Interleukin 17A) • IL23A (Interleukin 23 Subunit Alpha) • IL1B (Interleukin 1, beta) • IFNB1 (Interferon Beta 1)
    2years
    Huoxiang Zhengqi alleviates azoxymethane/dextran sulfate sodium-induced colitis-associated cancer by regulating Nrf2/NF-κB/NLRP3 signaling. (PubMed, Front Pharmacol)
    In conclusion, HXZQ alleviated CAC in mice by modulating the intestinal microbiota and metabolism, activating Nrf2-mediated antioxidant response, and inhibiting NF-κB-mediated NLRP3 inflammasome activation against inflammation. The present data provide a reference for the use of HXZQ as a therapeutic or combination agent for clinical CAC treatment.
    Journal
    |
    IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • HMOX1 (Heme Oxygenase 1) • IL10 (Interleukin 10) • NQO1 (NAD(P)H dehydrogenase, quinone 1) • IL17A (Interleukin 17A) • IL23A (Interleukin 23 Subunit Alpha) • IL1B (Interleukin 1, beta) • IL21 (Interleukin 21) • NLRP3 (NLR Family Pyrin Domain Containing 3) • CAT (Catalase)
    2years
    CRISPR/Cas9-mediated deletion of Interleukin-30 suppresses IGF1 and CXCL5 and boosts SOCS3 reducing prostate cancer growth and mortality. (PubMed, J Hematol Oncol)
    Membrane-anchored IL30 expressed by human PC cells shares a tumor progression programs with its murine homolog and, via juxtacrine signals, steers a complex network of PC driver and immunity genes promoting prostate oncogenesis. The efficacy of CRISPR/Cas9-mediated targeting of IL30 in curbing PC progression paves the way for its clinical use.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • BCL2 (B-cell CLL/lymphoma 2) • CCR4 (C-C Motif Chemokine Receptor 4) • IGF1 (Insulin-like growth factor 1) • PTGS2 (Prostaglandin-Endoperoxide Synthase 2) • TLR4 (Toll Like Receptor 4) • IL1A (Interleukin 1, alpha) • STAT1 (Signal Transducer And Activator Of Transcription 1) • CCR2 (C-C Motif Chemokine Receptor 2) • CXCL5 (Chemokine (C-X-C motif) ligand 5) • CXCR5 (C-X-C Motif Chemokine Receptor 5) • PACERR (PTGS2 Antisense NFKB1 Complex-Mediated Expression Regulator RNA) • SOCS3 (Suppressor Of Cytokine Signaling 3)
    2years
    Daphnetin alleviates experimental autoimmune encephalomyelitis by suppressing Th1 and Th17 cells and upregulating Th2 and regulatory T cells. (PubMed, Acta Neurobiol Exp (Wars))
    Moreover, the levels of IFN‑γ, TNF‑α, and IL‑17 displayed a noticeable reduction in the daphnetin treated group. Daphnetin appears to improve the disease by increasing the expression of anti‑inflammatory cytokines and transcription factors (IL‑4, IL‑10, IL‑33, GATA3, TGF‑β, FoxP3), and reducing the production of pro‑inflammatory cytokines and transcription factors (IFN‑γ, STAT4, T‑bet, IL‑17, STAT3, ROR‑γt, TNF‑α).
    Journal
    |
    IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • STAT3 (Signal Transducer And Activator Of Transcription 3) • TGFB1 (Transforming Growth Factor Beta 1) • FOXP3 (Forkhead Box P3) • GATA3 (GATA binding protein 3) • STAT4 (Signal Transducer And Activator Of Transcription 4)
    2years
    IL-12 and IL-27 upregulate CD39 expression on CD8+ T-cells and differentially affect CD39+CD8+ T-cell effector function (SITC 2022)
    Future experiments will assess the functionality of CD39 + CD8 + T-cells using ex vivo cytotoxicity assays. Data generated in this study will provide novel information on the mechanism of CD39 induction and its effect on CD8 + T-cell function, which can be exploited to improve future cancer therapies.
    IO biomarker
    |
    CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • IL2 (Interleukin 2) • LAMP1 (Lysosomal Associated Membrane Protein 1) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
    |
    CD8 expression • IFNG expression
    2years
    IL-27 expressed in the tumor microenvironment is correlated with PD-L1 levels and can induce PD-L1 expression on immune and tumor cells (SITC 2022)
    Blocking IL-27 activity by SRF388, a first-in-class monoclonal antibody, enhances immune function and demonstrates monotherapy activity in patients with cancer ( NCT04374877 )...IL-27 + cells are found in close proximity to PD-L1 + cells in patient tumors, and IL-27 can regulate levels of PD-L1 expression in immune cells and tumor cell lines, suggesting cross-talk between these molecules to diminish immune activation within the tumor microenvironment. Combined blockade of IL-27 and PD-(L)1 to enhance antitumor immune responses is currently being evaluated in clinical trials.
    PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • LAG3 (Lymphocyte Activating 3) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
    |
    PD-L1 expression • LAG3 expression • IL2RA expression
    |
    casdozokitug (CHS-388)
    over2years
    4-1BB antibody enhances cytotoxic activity of natural killer cells against prostate cancer cells via NKG2D agonist combined with IL-27. (PubMed, Immunotherapy)
    The combined treatment enhanced NK-cell cytotoxicity against both PC3 and DU145 cells with concurrent enhanced STAT3 activation. 4-1BB antibody and IL-27 improved NKG2D agonist function in NK cells against prostate cancer cells.
    Journal
    |
    IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • STAT3 (Signal Transducer And Activator Of Transcription 3) • IL10 (Interleukin 10) • KIR2DL1 (Killer Cell Immunoglobulin Like Receptor, Two Ig Domains And Long Cytoplasmic Tail 1) • NKG2D (killer cell lectin like receptor K1)
    |
    IFNG expression
    over2years
    Downregulation of STAT3 in Epstein-Barr Virus-Positive Hodgkin Lymphoma. (PubMed, Biomedicines)
    Taken together, this cell line deals with two conflicting oncogenic drivers, namely, JAK2-STAT3 signaling and EBV infection, but is sensitive to switch after cytokine stimulation. Thus, AM-HLH represents a unique cell line model to study the pathogenic roles of STAT3 and EBV and their therapeutic implications in HL.
    Journal
    |
    IL6 (Interleukin 6) • STAT3 (Signal Transducer And Activator Of Transcription 3) • MIR155 (MicroRNA 155) • IRF4 (Interferon regulatory factor 4)
    |
    STAT3 expression • miR-155 expression
    over2years
    Safety, recommended dose, efficacy and immune correlates for nintedanib in combination with pembrolizumab in patients with advanced cancers. (PubMed, J Exp Clin Cancer Res)
    Nintedanib 150 mg bid is the recommended dose for combination with pembrolizumab and is currently investigated in multiple expansion cohorts. Early tumoral and circulating immune factors were associated with cancer outcome under nintedanib & pembrolizumab therapy.
    Journal • Combination therapy
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    IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • CCR4 (C-C Motif Chemokine Receptor 4) • CD4 (CD4 Molecule) • LAMP3 (Lysosomal Associated Membrane Protein 3) • CCL2 (Chemokine (C-C motif) ligand 2) • FOXP3 (Forkhead Box P3) • CCL22 (C-C Motif Chemokine Ligand 22) • CXCR3 (C-X-C Motif Chemokine Receptor 3) • CXCR5 (C-X-C Motif Chemokine Receptor 5)
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    IL6-L
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    Keytruda (pembrolizumab) • nintedanib
    over2years
    Symptomatic Radiation Pneumonitis in NSCLC Patients Receiving EGFR-TKIs and Concurrent Once-daily Thoracic Radiotherapy: Predicting the Value of Clinical and Dose-volume Histogram Parameters. (PubMed, Zhongguo Fei Ai Za Zhi)
    Patients receiving both EGFR-TKIs and once-daily TRT were more likely to develop symptomatic RP than patients receiving concurrent chemoradiotherapy. The ilV30, tlV20, and comorbidity of COPD may predict the risk of symptomatic RP among NSCLC patients receiving EGFR-TKIs and conventionally fractionated TRT concurrently.
    Retrospective data • Journal
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    EGFR (Epidermal growth factor receptor)
    over2years
    "Derived Multiple Allogeneic Protein Paracrine Signaling (d-MAPPS)" Enhances T Cell-Driven Immune Response to Murine Mammary Carcinoma. (PubMed, Anal Cell Pathol (Amst))
    d-MAPPS in CXCL16-dependent manner promoted recruitment of antitumorigenic IFN-γ/IL-17-producing CD4+Th1/Th17 cells and in IL-27-dependent manner induced expansion of tumoricidal CD178+granzyme B-expressing CD8+CTLs and inhibited generation of tolerogenic DC, IL-10, and TGF-β-producing FoxP3-expressing T regulatory cells. In summing up, d-MAPPS, in CXL16- and IL-27-dependent manner, enhanced T cell-driven antitumor immune response and suppressed breast cancer growth in experimental mice.
    Preclinical • Journal • IO biomarker
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    CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD4 (CD4 Molecule) • FASLG (Fas ligand) • IL10 (Interleukin 10) • GZMB (Granzyme B) • TGFB1 (Transforming Growth Factor Beta 1) • FOXP3 (Forkhead Box P3) • IL17A (Interleukin 17A)
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    CD8 expression • MHC-II expression • FOXP3 expression