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Potentiating CAR-T cell function in the immunosuppressive tumor microenvironment by inverting the TGF-β signal.
Mol Ther
December 2024
Department of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Peking University, Beijing 100191, China; MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China; Shenzhen Stem Cell Engineering Laboratory, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China. Electronic address:
The immunosuppressive tumor microenvironment represents a key challenge for chimeric antigen receptor (CAR) T cells in solid tumors and includes the production of the inhibitory cytokine transforming growth factor β (TGF-β), which limits CAR-T cell persistence and function. Current strategies involving the blockade of TGF-β signaling have little benefit for solid tumor treatment. Here, we demonstrate a novel inverted cytokine receptor (ICR)-modified CAR-T cell strategy not only TGF-β signal blockade but also antitumor efficacy enhancement.
View Article and Find Full Text PDFAntitumor host immunity enhanced by near-infrared photoimmunotherapy.
Cancer Sci
December 2024
Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Near-infrared photoimmunotherapy (NIR-PIT) is a novel antitumor therapy that selectively kills cancer cells by NIR light-triggered photochemical reaction of IRDye700DX within Ab-photoabsorber conjugates (APCs). NIR-PIT induces immunogenic cell death, causing immune cell migration between the tumor and tumor-draining lymph nodes, and expanding multiclonal tumor-infiltrating CD8 T cells. Crucially, the cytotoxic effects of NIR-PIT are limited to cancer cells, sparing immune cells such as antigen-presenting cells and T cells, which are key players in boosting antitumor host immunity.
View Article and Find Full Text PDFEffect of hypoxia-induced mIL15 expression on expansion and memory progenitor stem-like TILs .
Front Immunol
December 2024
Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, China.
Introduction: The adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) has proven clinically beneficial in patients with non-small cell lung cancer refractory to checkpoint blockade immunotherapy, which has prompted interest in TIL-adoptive cell transfer. The transgenic expression of IL15 can promote the expansion, survival, and function of T cells and and enhance their anti-tumor activity. The effect of expressing mIL15 regulated by hypoxia in the tumor microenvironment on the expansion, survival, and stem-like properties of TILs has not been explored.
View Article and Find Full Text PDFAnti-CD8/IL-15 (N72D)/sushi fusion protein: A promising strategy for improvement of cancer immunotherapy.
Cytokine
January 2025
Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran; Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:
Background: To overcome the limitations of IL-15 and to improve the efficacy of IL-15 in immunotherapy, several strategies have been introduced.
Objective: The objective of this study was to generate and evaluate a novel anti-CD8/IL-15 (N72D)/Sushi fusion protein with the potential to target CD8 T cells and enhance functionality of CD8 T cells against tumor cells.
Methods: In this connection, a novel fusokine that contains IL-15(N72D), a Sushi domain, and anti-CD8 single-chain fragment variable (scFv) was designed.
Effect of omalizumab on inflammatory markers in COVID-19: an exploratory analysis of the COVID-19 immunologic antiviral therapy with omalizumab (CIAO) trial.
Front Med (Lausanne)
November 2024
Faculty of Medicine, McGill University, Montreal, QC, Canada.
Background: The CIAO trial recently demonstrated a probable clinical benefit of omalizumab in the treatment of severe COVID-19; however, the mechanism underlying this benefit remains unclear. Therefore, we sought to longitudinally assess the impact of omalizumab on serum cytokines in CIAO trial patients to determine its mechanism of action.
Methods: Blood samples were collected on days 0, 2, 7, and 14 from patients recruited into the CIAO trial and who consented to this substudy.
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