In cancer immunotherapy, the use of dendritic cells (DC) loaded with tumor-associated antigens (TAA) emerged as a promising strategy. We initiated 3 pilot clinical trials with immunological endpoints using TAA loaded autologous DC. These trials showed that this approach was safe and associated with the induction of potent TAA specific IFN-gamma responses, which were transient despite the providing a further help through KLH presentation. Subcutaneous (s.c.) IL-2 administration was associated with long-lasting TAA specific IL-5 production. Clinical responses were observed in about 1/3 of the patients. Further improvements will take advantage of the use of a new type of DC cells (IL-3/IFN-beta DC) and of tumor cell-DC hybrids.
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Introduction: The pathogenic role of nitric oxide (NO) signaling during development of thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) is currently unclear. We characterized vasomotor function and its relationship to the activity of the NO-generating enzymes in mice with early onset progressively severe MFS.
Methods: Wire myography, immunoblotting, measurements of aortic NO and superoxide levels were used to compare vasomotor function, contractile-protein levels, and the activity of endothelial and inducible NO synthase (eNOS and iNOS, respectively) in ascending thoracic aortas of Fbn1mgR/mgR mice relative to wild type (WT) littermates.
J Clin Invest
January 2025
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
The pathogenesis of thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) is generally attributed to vascular smooth muscle cell (VSMC) pathologies. However, the role of immune cell-mediated inflammation remains elusive. Single-cell RNA sequencing identified a subset of CX3CR1+ macrophages mainly located in the intima in the aortic roots and ascending aortas of Fbn1C1041G/+ mice, further validated in MFS patients.
View Article and Find Full Text PDFJ Am Acad Orthop Surg
November 2024
From the Medical University of South Carolina, Charleston, SC (Gross and Scott), the University of California Irvine, Orange, CA (Hsu), and the Palomar Health Medical Group, San Diego, CA (Palanca).
The design of total ankle arthroplasty (TAA) systems is rapidly evolving as device companies try to keep pace with the expansion of surgical indications and a refinement of techniques for TAA. Even since the publication of the latest "update," published in 2018, three new designs and three updates on preexisting third-generation implants came onto the market. Improvements in third-generation TAA systems include minimal bone resection, retaining ligamentous support, and anatomic balancing.
View Article and Find Full Text PDFmBio
January 2025
Antimicrobial Resistance, Omics and Microbiota Group, Centre for Systems Health and Integrated Metabolic Research, Department of Biosciences, Nottingham Trent University, Nottingham, United Kingdom.
is an unusual diderm firmicute that plays a central role in the formation of dental biofilm formation through coaggregation with many other oral bacteria. However, the molecular interactions leading to oral biofilm formation are largely unknown. In a recent study (L.
View Article and Find Full Text PDFFront Immunol
January 2025
Molecular Immunology and Gene Therapy, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Generation of high avidity T cell receptors (TCRs) reactive to tumor-associated antigens (TAA) is impaired by tolerance mechanisms, which is an obstacle to effective T cell therapies for cancer treatment. NY-ESO-1, a human cancer-testis antigen, represents an attractive target for such therapies due to its broad expression in different cancer types and the restricted expression in normal tissues. Utilizing transgenic mice with a diverse human TCR repertoire, we isolated effective TCRs against NY-ESO-1 restricted to HLA-A*02:01.
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