OVATION-2: A randomized phase I/II study evaluating the safety and efficacy of IMNN-001 (IL-12 gene therapy) with neo/adjuvant chemotherapy in patients newly-diagnosed with advanced epithelial ovarian cancer DOI Creative Commons
Premal H. Thaker, Debra L. Richardson, Andrea R. Hagemann

и другие.

Gynecologic Oncology, Год журнала: 2025, Номер unknown

Опубликована: Июнь 1, 2025

OVATION-2, a randomized, controlled, open label phase 1/2 study, evaluated the safety and efficacy of IMNN-001, an IL-12 immune gene therapy, with neo/adjuvant chemotherapy (N/ACT) compared to N/ACT in newly-diagnosed advanced epithelial ovarian cancer (EOC). IMNN-001 is immunotherapeutic nanoparticle comprising DNA plasmid encoding encased lipopolymer. High-grade EOC patients were randomized 1:1 carboplatin/paclitaxel IV every 21 days for 3 cycles, before after interval debulking surgery (IDS) or intraperitoneal (IP) given weekly concurrently 8 weeks 9 IDS. 54 58 predominantly Stage IIIC/IV control experimental arm, respectively. Primary endpoints PFS. Overall, arm was well tolerated gastrointestinal cytopenias as most common TEAEs no CRS elevated risk events. PFS 14.9 months (mo) vs 11.9 mo; HR 0.79 (95 % CI: 0.51-1.23). Secondary included OS (46.0 mo 33.0 0.69 (CI: 0.40-1.19)) surgical response R0 rate (64.6 52.1 %). For who received PARPi maintenance, 33.8 22.1 0.80 0.31-2.12) NE 37.1 0.38 0.13-1.06) both favoring arm. The addition shows promising numerical 13-mo benefit on survival acceptable profile EOC.

Язык: Английский

Combined Immune Checkpoint Blockade and Helixor® Therapy in Oncology: Real-World Tolerability and Subgroup Survival (ESMO GROW) DOI Open Access
Anja Thronicke, Patricia Grabowski,

J.A.D.M. De Roos

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3669 - 3669

Опубликована: Апрель 12, 2025

Real-world data (RWD) play a crucial role in identifying key subgroups and assessing multimodal oncology therapies, including integrative palliative care. Immune checkpoint blockade (ICB) has improved survival, its combination with complementary therapies like Viscum album L. extracts (VA) may enhance outcomes. This RWD study, based on the Network Oncology registry ESMO-GROW guidelines, analyzed oncological patients receiving PD-1/PD-L1 inhibitors alone or Helixor® VA (HVA) extracts. Primary secondary objectives were tolerability overall survival. Statistical analyses included Kaplan–Meier survival curves Cox regression. Among 405 cancer patients, 344 received ICB (CTRL) 61 + HVA (COMB). Lung was predominant (78.6%). Adverse event-related discontinuation lower COMB (4.9% vs. 6.4%, p = 0.25). In non-small cell lung (NSCLC) 3-year rate significantly higher (34.3% 17.2%, 0.02). female NSCLC associated reduced death risk of 91.2% (aHR: 0.088; 95% CI: 0.009–0.783). Our findings show favorable combinatorial several tumor entities underscore potential to improve particularly warranting further investigation.

Язык: Английский

Процитировано

0
Deubiquitinase USP24 activated by IL-6/STAT3 enhances PD-1 protein stability and suppresses T cell antitumor response DOI Creative Commons

Hung-Chia Hsieh,

Ming-Jer Young, Kuan‐Yu Chen

и другие.

Science Advances, Год журнала: 2025, Номер 11(16)

Опубликована: Апрель 16, 2025

Persisting programmed cell death-1 (PD-1) signaling impairs T effector function, which is highly associated with exhaustion and immunotherapy failure. However, the mechanism responsible for PD-1 deubiquitination dysfunction remains unclear. Here, we show that ubiquitin-specific peptidase 24 (USP24) promotes protein stability by removing K48-linked polyubiquitin. Increased interleukin-6 level transcriptionally activates USP24 expression, leads to stabilization. Furthermore, deficiency reduces levels in CD8 + cells attenuates Egfr L858R -driven lung tumorigenesis Usp24 C1695A catalytic deficient mice. Targeting USP24-specific inhibitor USP24-i-101 boosts cytotoxic activity, restrains tumor growth, achieves superior therapeutic effects when combined anti-CTLA4 immunotherapy. Clinically, patients cancer exhibiting high expression tumor-infiltrating display exhausted features unfavorable responses Our findings dissect regulating enhanced reveal as a potential target of antitumor

Язык: Английский

Процитировано

0
Thrombospondin-1 induces immunogenic cell death in human mucoepidermoid carcinoma MC-3 cells via the PERK/eIF2α signaling pathway: potential implications for tumor immunotherapy DOI Creative Commons
Yixuan Zhu,

Kaizhi Cai,

Lijuan Guo

и другие.

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 19, 2025

To investigate whether Thrombospondin-1 (TSP-1) induces immunogenic cell death (ICD) in human mucoepidermoid carcinoma (MC-3) cells and explore its potential to induce calreticulin (CRT) exposure via the PERK/eIF2α signaling pathway. The MC-3 line was used as research model. CCK-8 assay performed determine optimal seeding density, TSP-1 concentration, treatment time. Annexin V/PI double staining combined with flow cytometry assess apoptosis across different experimental groups (blank control, TSP-1, paclitaxel (PTX), + PTX). Cells were divided into groups: blank PTX, ISRIB (ISRIB: Integrated Stress Response Inhibitor), CRT expression detected by cytometry. Immunofluorescence, Western blot, qPCR detect of PERK (Protein Kinase R-like Endoplasmic Reticulum Kinase), eIF2α (eukaryotic Initiation Factor 2α), CRT. All experiments triplicate, data analyzed using GraphPad Prism 8.0 software. Statistical significance set at P < 0.05. At a density 2 × 104/mL, reached growth plateau day six. concentration duration 0.1 μmol/L 72 h, respectively. Flow cytometry, immunofluorescence, results revealed that significantly induced (P 0.05), accompanied upregulation 0.05). Co-treatment PTX further enhanced these effects, while addition reduced PERK, eIF2α, ICD cells, exposure, potentially mediated through activation These findings suggest may have an adjunct chemotherapy for enhancing tumor immunotherapy.

Язык: Английский

Процитировано

0
Combination of radiotherapy and ICIs in advanced hepatocellular carcinoma: A systematic review of current evidence and future prospects (Review) DOI Open Access
Cheng Ma,

Xinlin Yu,

Xialin Zhang

и другие.

Oncology Letters, Год журнала: 2025, Номер 30(1), С. 1 - 15

Опубликована: Май 14, 2025

Hepatocellular carcinoma (HCC) is a global health concern because of its rising prevalence and high fatality rates. Conventional treatments for advanced HCC (aHCC) have limited success, emphasizing the need novel treatment options. Radiotherapy (RT) treatments, such as stereotactic body radiation proton therapy, improve local tumor management via precision targeting. Moreover, immune checkpoint inhibitors (ICIs) that target programmed cell death protein 1(PD-1)/PD ligand 1 (PD-L1) cytotoxic T lymphocyte associated 4 (CTLA-4) pathways promise systemic antitumor effectiveness. The combination RT ICIs takes advantage their complementary mechanisms: kills immunogenic cells controls microenvironment to increase antigen presentation, whereas enhance maintain responses. This enhances regression response in aHCC, improving rate progression-free survival with manageable safety. present review aimed summarize rationale combining + patients aHCC clinical outcomes, well ways this technique. these models promising technique outcomes warrants further investigation.

Язык: Английский

Процитировано

0
OVATION-2: A randomized phase I/II study evaluating the safety and efficacy of IMNN-001 (IL-12 gene therapy) with neo/adjuvant chemotherapy in patients newly-diagnosed with advanced epithelial ovarian cancer DOI Creative Commons
Premal H. Thaker, Debra L. Richardson, Andrea R. Hagemann

и другие.

Gynecologic Oncology, Год журнала: 2025, Номер unknown

Опубликована: Июнь 1, 2025

OVATION-2, a randomized, controlled, open label phase 1/2 study, evaluated the safety and efficacy of IMNN-001, an IL-12 immune gene therapy, with neo/adjuvant chemotherapy (N/ACT) compared to N/ACT in newly-diagnosed advanced epithelial ovarian cancer (EOC). IMNN-001 is immunotherapeutic nanoparticle comprising DNA plasmid encoding encased lipopolymer. High-grade EOC patients were randomized 1:1 carboplatin/paclitaxel IV every 21 days for 3 cycles, before after interval debulking surgery (IDS) or intraperitoneal (IP) given weekly concurrently 8 weeks 9 IDS. 54 58 predominantly Stage IIIC/IV control experimental arm, respectively. Primary endpoints PFS. Overall, arm was well tolerated gastrointestinal cytopenias as most common TEAEs no CRS elevated risk events. PFS 14.9 months (mo) vs 11.9 mo; HR 0.79 (95 % CI: 0.51-1.23). Secondary included OS (46.0 mo 33.0 0.69 (CI: 0.40-1.19)) surgical response R0 rate (64.6 52.1 %). For who received PARPi maintenance, 33.8 22.1 0.80 0.31-2.12) NE 37.1 0.38 0.13-1.06) both favoring arm. The addition shows promising numerical 13-mo benefit on survival acceptable profile EOC.

Язык: Английский

Процитировано

0