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CD40 provides signals crucial to the activation of antigen-presenting cells during humoral and cell-mediated immune responses. A complex cohort of proteins interacts with the cytoplasmic domain of CD40 and mediates signaling. One member of this cohort is TNF receptor associated factor six (TRAF6). TRAF6 contributes to the CD40-mediated activation of NF-kappaB, stress-activated protein kinases, and perhaps other signaling molecules. TRAF6 may have roles as an adapter molecule, an activator of mitogen-activated protein kinases, and as a repressor of certain signaling circuits. Establishing the significance and interplay of these roles will lead to a more complete understanding of mechanisms important to the CD40-mediated activation of the immune system and will reveal novel targets for the development of therapeutic agents.
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http://dx.doi.org/10.1007/s12026-007-0082-3 | DOI Listing |
JHEP Rep
September 2024
Department of Immunology & Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
Background & Aims: HBV treatment is challenging due to the persistence of the covalently closed circular DNA replication pool, which remains unaffected by antiviral intervention. In this study, we determined whether targeting antigen-presenting cells via CD40 stimulation represents an appropriate therapeutic approach for achieving sustained HBV control in a mouse model of HBV replication.
Methods: Mice were transduced with an adeno-associated virus encoding the HBV genome (AAV-HBV) to initiate HBV replication and were administered agonistic CD40 antibody.
Blood Adv
September 2024
Department of Hematology, Cancer Center Amsterdam, Lymphoma and Myeloma Center Amsterdam, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Autologous T-cell-based therapies, such as chimeric antigen receptor (CAR) T-cell therapy, exhibit low success rates in chronic lymphocytic leukemia (CLL) and correlate with a dysfunctional T-cell phenotype observed in patients. Despite various proposed mechanisms of T-cell dysfunction in CLL, the specific CLL-derived factors responsible remain unidentified. This study aimed to investigate the mechanisms through which CLL cells suppress CAR T-cell activation and function.
View Article and Find Full Text PDFAntibodies (Basel)
April 2024
Icanomab, Tassilostr. 2, 82398 Polling, Germany.
The activation of CD40-mediated signaling in antigen-presenting cells is a promising therapeutic strategy to promote immune responses against tumors. Most agonistic anti-CD40 antibodies currently in development require the Fcγ-receptor (FcγR)-mediated crosslinking of CD40 molecules for a meaningful activation of CD40 signaling but have limitations due to dose-limiting toxicities. Here we describe the identification of CD40 antibodies which strongly stimulate antigen-presenting cells in an entirely FcγR-independent manner.
View Article and Find Full Text PDFJ Cell Mol Med
April 2024
Department of Immunology, Genetics and Pathology (IGP), Science for Life Laboratories, Uppsala University, Uppsala, Sweden.
Immunostimulatory gene therapy using oncolytic viruses is currently evaluated as a promising therapy for cancer aiming to induce anti-tumour immunity. Here, we investigate the capacity of oncolytic adenoviruses (LOAd) and their transgenes to induce immunogenicity in the infected tumour cells. Oncolysis and death-related markers were assessed after infection of eight human solid cancer cell lines with different LOAd viruses expressing a trimerized, membrane-bound (TMZ)-CD40L, TMZ-CD40L and 41BBL, or no transgenes.
View Article and Find Full Text PDFN Biotechnol
March 2024
KTH - Royal Institute of Technology, School of Engineering Sciences in Chemistry, Biotechnology, and Health, Dept. of Protein Science, SE-106 91 Stockholm, Sweden. Electronic address:
Cancer immunotherapy, where a patient's immune system is harnessed to eradicate cancer cells selectively, is a leading strategy for cancer treatment. However, successes with immune checkpoint inhibitors (ICI) are hampered by reported systemic and organ-specific toxicities and by two-thirds of the patients being non-responders or subsequently acquiring resistance to approved ICIs. Hence substantial efforts are invested in discovering novel targeted immunotherapies aimed at reduced side-effects and improved potency.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!