Abstract:Humans and mice deficient in Fas, a tumor necrosis factor (TNF)-receptor family member, cannot induce apoptosis of autoreactive cells, and consequently develop progressive lymphoproliferative disorders and lupus-like autoimmune diseases. Previous studies have shown that short-term administrations of agonistic monoclonal antibodies against CD137, another TNF-receptor family member, activate T cells and induce rejection of allografts and established tumors. Here we report that treatment with an agonistic monoclo… Show more
“…Other autoimmunity models, however, confirm this paradox. For example, systemic lupus erythematosus (SLE) is inhibited after enforcing CD137 co-stimulation [45,46], as is arthritis [47,48] and uveitis [49]. Not all autoimmunity models respond identically, however, because transgenic …”
Section: Role Of Cd137 During Autoimmunitymentioning
“…Other autoimmunity models, however, confirm this paradox. For example, systemic lupus erythematosus (SLE) is inhibited after enforcing CD137 co-stimulation [45,46], as is arthritis [47,48] and uveitis [49]. Not all autoimmunity models respond identically, however, because transgenic …”
Section: Role Of Cd137 During Autoimmunitymentioning
“…• One important question raised with any immunomodulatory agent destined for clinical application is the potential for induction of autoimmunity. Agonistic mAbs against CD137 may enhance antitumor immune reactivity while ameliorating autoimmune diseases in mouse models [20]. Mice with the Fas gene mutation (lpr) develop a syndrome analogous to human systemic lupus erythematosis, characterized by spontaneous lymphoproliferation, hypergammaglobulinemia, and immune complex-mediated renal failure.…”
Section: Emerging Therapiesmentioning
confidence: 99%
“…Treatment of these mice with agonistic mAbs against CD137 inhibits disease initiation and prolongs survival. Although the mechanism for these effects is not fully elucidated, it is likely secondary to deletion of autoreactive double-negative T cells and B cells [20]. Although these data require clinical correlation, they suggest that CD137 mAb therapy may not stimulate ongoing autoimmunity mediated by CD4+ T cells and these mAbs may serve as a therapeutic option for select patients with rheumatic disease.…”
Section: Emerging Therapiesmentioning
confidence: 99%
“…Because of the relative low affinity of CD137L binding in comparison to agonistic mAbs, mAbs are postulated to have greater potential for clinical application. Recent trends have centered on the use of fully human antibodies, generated from gene targeted recombinant mice or molecular cloning [20,21]. There are two primary reasons that fully humanized mAbs are advantageous for clinical application: decreased potential for the development of neutralizing antibodies against nonhuman components and increased serum half-life of chimeric or fully humanized antibodies in comparison to antibodies of murine origin [22].…”
Squamous cell carcinoma of the head and neck (SCCHN) is an important source of cancer-related morbidity and mortality worldwide. Current treatment options are founded on various combinations of surgery, radiation therapy, and chemotherapy, with implementation largely based on patient/disease-specific factors and provider/institutional bias. Despite improvements in surgical techniques and the development of novel chemoradiotherapy strategies for organ preservation, survival has remained relatively unchanged in the past 30 years. Additionally, the impact of these novel treatment approaches on the quality of life of patients remains largely unknown. Improvements in survival and the quality of life for patients with SCCHN will likely require the development of new therapeutic alternatives based on the improved understanding of the molecular pathogenesis of SCCHN and associated changes in the immune response.
“…15,16 Very little is known regarding CD137 expression in steady state conditions in human tissues. Here, we immunostained secondary lymphoid organs to ascertain which cell subsets and histological compartments express CD137 in healthy conditions or under naturally occurring inflammation.…”
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