A high recurrence rate of non-Hodgkin's lymphoma (NHL) following chimeric antigen receptor T (CAR T) cell treatment remains a bottleneck, and immunosuppressive tumor microenvironment (TME) compromising CAR T cell efficacy in NHL is the primary cause of relapse. Accordingly, modifying the structure of CAR T cells to attenuate the inhibitory effect of TME thus reducing recurrence rate is a valuable research topic. CD47 has been proved to be a promising therapeutic target and is crucial in regulating macrophage function. Herein, we engineered CD19-CAR T cells to secrete an anti-CD47 single-chain variable fragment (scFv) and validated their function in enhancing antitumor efficacy, regulating T cells differentiation, modifying phagocytosis and polarization of macrophages by and researches. The efficacy was analogous or preferable to the combination of CAR T cells and CD47 antibody. Of note, anti-CD47 scFv secreting CAR T cells exert a more potent immune response following specific antigen stimulation compared with parental CAR T cells, characterized by more efficient degranulation and cytokine production with polyfunctionality. Furthermore, locally delivering anti-CD47 by CAR T cells potentially limits toxicities relevant to systemic antibody treatment. Collectively, our research provides a more effective and safer CAR T cell transformation method for enhancing tumor immunotherapy.
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http://dx.doi.org/10.7150/ijbs.86632 | DOI Listing |
Biomaterials
December 2024
School of Engineering, Vanderbilt University, Nashville, TN, 37235, USA. Electronic address:
Multiple myeloma (MM), a cancer of bone marrow plasma cells, is the second-most common hematological malignancy. However, despite immunotherapies like chimeric antigen receptor (CAR)-T cells, relapse is nearly universal. The bone marrow (BM) microenvironment influences how MM cells survive, proliferate, and resist treatment.
View Article and Find Full Text PDFNat Biomed Eng
December 2024
The Koch Institute for Integrative Cancer Research, Cambridge, MA, USA.
Curr Res Transl Med
December 2024
Thermo Fisher Scientific, 5781 Van Allen Way, Carlsbad CA 92008, USA. Electronic address:
The traditional method of CAR T cell production involves lengthy ex-vivo culture times which can result in the reduction of crucial naïve T cell subsets. Moreover, traditional CAR T cell therapy manufacturing processes can prolong time-to-patient, potentially delaying patient treatment, and contribute to disease progression. In this study, we describe an innovative and semi-automated 24-hour CAR T manufacturing process that yields a higher percentage of naïve/stem-cell like T cells which showed high cytotoxic activity and cytokine release in vitro.
View Article and Find Full Text PDFWorld J Microbiol Biotechnol
December 2024
Department of Bioengineering and Biotechnology, Huaqiao University, Xiamen, 361021, China.
Heavy metal and nitrogen contaminations are serious concerns in aquatic environments. Marichromatium gracile YL28, a marine purple sulfur bacterium, has shown great potential as a bioremediation agent for removing inorganic nitrogen from marine water. This study further investigated its ability to simultaneously absorb heavy metals, including Pb(II), Cu(II), Cd(II) and Cr(VI), and remove inorganic nitrogen.
View Article and Find Full Text PDFHaematologica
December 2024
Medical University of Warsaw, Warsaw, Poland; Senior authors.
Our investigation uncovers that nanomolar concentrations of salinomycin, monensin, nigericin, and narasin (a group of potassium/sodium cation carriers) robustly enhance surface expression of CD20 antigen in B-cell-derived tumor cells, including primary malignant cells of chronic lymphocytic leukemia and diffuse large B-cell lymphoma. Experiments in vitro, ex vivo, and animal model reveal a novel approach of combining salinomycin or monensin with therapeutic anti-CD20 monoclonal antibodies or anti-CD20 CAR-T cells, significantly improving non- Hodgkin lymphoma (NHL) therapy. The results of RNA-seq, genetic editing, and chemical inhibition delineate the molecular mechanism of CD20 upregulation, at least partially, to the downregulation of MYC, the transcriptional repressor of the MS4A1 gene encoding CD20.
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