ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Phase I Trial Combining Chemokine-Targeting with Loco-Regional Chemoimmunotherapy for Recurrent, Platinum-Sensitive Ovarian Cancer Shows Induction of CXCR3 Ligands and Markers of Type 1 Immunity.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02432378 (A PHASE 2 EFFICACY TRIAL OF INTENSIVE LOCOREGIONAL CHEMOIMMUNOTHERAPY FOR ADVANCED STAGE OVARIAN CANCER AND TUMOR-SPECIFIC INTRANODAL AUTOLOGOUS ALPHA-DC1 VACCINES), which is not on this map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A phase 2 efficacy trial of intensive locoregional chemoimmunotherapy for advanced stage ovarian cancer and tumor-specific intranodal autologous alpha-dc1 vaccines
Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
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- The Reign of Follistatin in Tumors and Their Microenvironment: Implications for Drug Resistance.Biology · 2024Review
- Article
- Systemic infusion of TLR3-ligand and IFN-α in patients with breast cancer reprograms local tumor microenvironments for selective CTL influx.Journal for immunotherapy of cancer · 2023Article
- CT radiomics prediction of CXCL9 expression and survival in ovarian cancer.Journal of ovarian research · 2023Article
- Two Modes of Th1 Polarization Induced by Dendritic-Cell-Priming Adjuvant in Vaccination.Cells · 2023Review
- Quiescent Ovarian Cancer Cells Secrete Follistatin to Induce Chemotherapy Resistance in Surrounding Cells in Response to Chemotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Intracavitary adoptive transfer of IL-12 mRNA-engineered tumor-specific CD8Oncoimmunology · 2023Article
- Review
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeIncreased prevalence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts positive outcomes in patients with epithelial ovarian cancer (EOC), whereas the regulatory T cells (Treg) predict poor outcomes. Guided by the synergistic activity of TLR3 ligands, IFNα, and COX-2 blockers in selectively enhancing CTL-attractants but suppressing Treg-attractants, we tested a novel intraperitoneal chemoimmunotherapy combination (CITC), to assess its tolerability and TME-modulatory impact in patients with recurrent EOC. PATIENTS AND
methodsTwelve patients were enrolled in phase I portion of the trial NCT02432378, and treated with intraperitoneal cisplatin, intraperitoneal rintatolimod (dsRNA, TLR3 ligand), and oral celecoxib (COX-2 blocker). Patients in cohorts 2, 3, and 4 also received intraperitoneal IFNα at 2, 6, and 18 million units (MU), respectively. Primary objectives were to evaluate safety, identify phase 2 recommended dose (P2RD), and characterize changes in the immune TME. Peritoneal resident cells and intraperitoneal wash fluid were profiled via NanoString and Meso Scale Discovery (MSD) multiplex assay, respectively.
resultsThe P2RD of IFNα was 6 MU. Median progression-free survival and overall survival were 8.4 and 30 months, respectively. Longitudinal sampling of the peritoneal cavity via intraperitoneal washes demonstrated local upregulation of IFN-stimulated genes (ISG), including CTL-attracting chemokines (CXCL-9, -10, -11), MHC I/II, perforin, and granzymes. These changes were present 2 days after chemokine modulation and subsided within 1 week.
conclusionsThe chemokine-modulating intraperitoneal-CITC is safe, tolerable, and associated with ISG changes that favor CTL chemoattraction and function. This combination (plus DC vaccine) will be tested in a phase II trial. See related commentary by Aranda et al., p. 1993.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.