Solid tumours can be eradicated by infusion of large amounts of tumour-specific T-cells in animal models. The successes seen in preclinical models, however, have not been adequately translated to human disease due, in part, to the inability to expand tumour antigen-specific T-cells ex vivo. Polyclonality and retention of antigen-specificity are two important properties of infused T-cells that are necessary for successful eradication of tumours. Investigators are beginning to evaluate the impact of attempting to reconstitute full T-cell immunity representing both major T-cell subsets, cytolytic T-cells and T-helper (Th) cells. One of the more important and often overlooked steps of successful adoptive T-cell therapy is the ex vivo expansion conditions, which can dramatically alter the phenotype of the T-cell. A number of cytokines and other soluble activation factors that have been characterised over the last decade are now available to supplement in vitro antigen presentation and IL-2. Newer molecular techniques have been developed and are aimed at genetically altering the characteristics of T-cells including their antigen-specificity and growth in vivo. In addition, advanced imaging techniques, such as positron emission tomography (PET), are being implemented in order to better define the in vivo function of ex vivo expanded tumour-specific T-cells.
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http://dx.doi.org/10.1517/14712598.2.1.55 | DOI Listing |
J Neuroinflammation
January 2025
Department of Neurology, Division of Neuroimmunology, School of Medicine, Johns Hopkins University, Baltimore, MD, 21287, USA.
Chronic innate immune activation in the central nervous system (CNS) significantly contributes to neurodegeneration in progressive multiple sclerosis (MS). Using multiple experimental autoimmune encephalomyelitis (EAE) models, we discovered that NLRX1 protects neurons in the anterior visual pathway from inflammatory neurodegeneration. We quantified retinal ganglion cell (RGC) density and optic nerve axonal degeneration, gliosis, and T-cell infiltration in Nlrx1 and wild-type (WT) EAE mice and found increased RGC loss and axonal injury in Nlrx1 mice compared to WT mice in both active immunization EAE and spontaneous opticospinal encephalomyelitis (OSE) models.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Rapa Therapeutics, Rockville, Maryland, USA.
Background: Polyclonal autologous T cells that are epigenetically reprogrammed through mTOR inhibition and IFN-α polarization (RAPA-201) represent a novel approach to the adoptive T cell therapy of cancer. Ex vivo inhibition of mTOR results causes a shift towards T central memory (T) whereas ex vivo IFN-α promotes type I cytokines, with each of these functions known to enhance the adoptive T cell therapy of cancer. Rapamycin-resistant T cells polarized for a type II cytokine phenotype were previously evaluated in the allogeneic transplantation context.
View Article and Find Full Text PDFAnn Rheum Dis
January 2025
Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany. Electronic address:
Objectives: CD19-targeting chimeric antigen receptor (CAR) T-cell therapy can induce long-term drug-free remission in patients with autoimmune diseases (AIDs). The efficacy of CD19-CAR T-cell therapy is presumably based on deep tissue depletion of B cells; however, such effect has not been proven in humans in vivo.
Methods: Sequential ultrasound-guided inguinal lymph node biopsies were performed at baseline and after CD19-CAR T-cell therapy in patients with AIDs.
Front Immunol
January 2025
Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, China.
Background: Chimeric antigen receptor T (CAR-T) cell therapy is more effective in relapsed or refractory diffuse large B cell lymphoma (DLBCL) than other therapies, but a high proportion of patients relapse after CAR-T cell therapy owing to antigen escape, limited persistence of CAR-T cells, and immunosuppression in the tumor microenvironment. CAR-T cell exhaustion is a major cause of relapse. Epigenetic modifications can regulate T cell activation, maturation and depletion; they can be applied to reduce T cell depletion, improve infiltration, and promote memory phenotype formation to reduce relapse after CAR-T cell therapy.
View Article and Find Full Text PDFCancer Rep (Hoboken)
January 2025
Department of Adult Lymphoma, Beijing Boren Hospital, Beijing, China.
Objective: Currently, chimeric antigen receptor T-cell (CART) therapy represents a highly effective approach for relapsed/refractory B-cell lymphomas. However, it also carries treatment-related risks. Limited data are available on the risks associated with CART therapy in patients with gastrointestinal involvement in B-cell lymphomas.
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