Suppression of an anti-tumor immune response by regulatory T cells (T(regs)) in tumor-bearing hosts is now well established. Previously, we have reported that the intratumoral administration of T(reg)-depleting anti-CD25 monoclonal antibody every 10 days is highly effective at inhibiting the further development of established murine mesotheliomas. Here we investigate the dosage, kinetics, and immunology of this treatment. Further, we show that by precisely timing neutralization of transforming growth factor-β (TGF-β) within treated tumors using a TGF-β-soluble receptor, the efficacy of the treatment can be significantly improved, resulting in tumor regression. We suggest that this combined intratumoral treatment approach can be applied clinically for the treatment of mesothelioma.
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http://dx.doi.org/10.1089/jir.2008.0055 | DOI Listing |
Nat Commun
January 2025
Carisma Therapeutics Inc, Philadelphia, PA, USA.
We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we develop clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduce tumor burden, prolong survival, remodel the TME, increase intratumoral T cell and natural killer (NK) cell infiltration, and induce antigen spreading.
View Article and Find Full Text PDFAcad Radiol
January 2025
Department of Radiology, Luzhou People's Hospital, Luzhou 646000, China (S.Z., J.C., A.R., X.Z., J.H., M.Y., F.W.). Electronic address:
Rationale And Objectives: Inflammation and immune biomarkers can promote angiogenesis and proliferation and metastasis of esophageal squamous cell carcinoma (ESCC). The degree of pathological grade reflects the tumor heterogeneity of ESCC. The purpose is to develop and validate a nomogram based on enhanced CT multidimensional radiomics combined with inflammatory immune score (IIS) for predicting poorly differentiated ESCC.
View Article and Find Full Text PDFActa Pharm Sin B
December 2024
School of Pharmacy, Institute of Hepatology and Metabolic Diseases, Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, China.
Specific tumor-targeted gene delivery remains an unsolved therapeutic issue due to aberrant vascularization in tumor microenvironment (TME). Some bacteria exhibit spontaneous chemotaxis toward the anaerobic and immune-suppressive TME, which makes them ideal natural vehicles for cancer gene therapy. Here, we conjugated ZIF-8 metal-organic frameworks encapsulating eukaryotic murine interleukin 2 () expression plasmid onto the surface of VNP20009, an attenuated strain with well-documented anti-cancer activity, and constructed a TME-targeted delivery system named /ZIF-8@.
View Article and Find Full Text PDFBMJ Open
December 2024
University College London Hospitals NHS Foundation Trust, London, UK
Introduction: Adaptive ChemoTherapy for Ovarian cancer (ACTOv) is a phase II, multicentre, randomised controlled trial, evaluating an adaptive therapy (AT) regimen with carboplatin in women with relapsed, platinum-sensitive high-grade serous or high-grade endometrioid cancer of the ovary, fallopian tube and peritoneum whose disease has progressed at least 6 months after day 1 of the last cycle of platinum-based chemotherapy. AT is a novel, evolutionarily informed approach to cancer treatment, which aims to exploit intratumoral competition between drug-sensitive and drug-resistant tumour subpopulations by modulating drug dose according to a patient's own response to the last round of treatment. ACTOv is the first clinical trial of AT in this disease setting.
View Article and Find Full Text PDFAm J Cancer Res
December 2024
Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University Providence, RI 02903, USA.
Androgen receptor (AR) signaling is a target in prostate cancer therapy and can be treated with non-steroidal anti-androgens (NSAA) including enzalutamide, and apalutamide for patients with advanced disease. Metastatic castration-resistant prostate cancer (mCPRC) develop resistance becomes refractory to therapy limiting patient overall survival. Darolutamide is a novel next-generation androgen receptor-signaling inhibitor that is FDA approved for non-metastatic castration resistant prostate cancer (nmCRPC).
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