Topic
Antigen
About: Antigen is a research topic. Over the lifetime, 170233 publications have been published within this topic receiving 6982342 citations. The topic is also known as: antibody generator & Antigen.
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TL;DR: In this article, the authors estimate the probability that an immune system with N Ab monospecific antibodies in its repertoire can recognize a random foreign antigen, and they conclude that multispecific recognition is a more reliable method of distinguishing between molecules than single site recognition.
640 citations
TL;DR: The determination of the main factors implicated in the lack of preexisting tumor T cell infiltration is crucial for the development of adapted algorithms of treatments for cold tumors.
Abstract: Therapeutic monoclonal antibodies targeting immune checkpoints (ICPs) have changed the treatment landscape of many tumors. However, response rate remains relatively low in most cases. A major factor involved in initial resistance to ICP inhibitors is the lack or paucity of tumor T cell infiltration, characterizing the so-called "cold tumors." In this review, we describe the main mechanisms involved in the absence of T cell infiltration, including lack of tumor antigens, defect in antigen presentation, absence of T cell activation and deficit of homing into the tumor bed. We discuss then the different therapeutic approaches that could turn cold into hot tumors. In this way, specific therapies are proposed according to their mechanism of action. In addition, ''supra-physiological'' therapies, such as T cell recruiting bispecific antibodies and Chimeric Antigen Receptor (CAR) T cells, may be active regardless of the mechanism involved, especially in MHC class I negative tumors. The determination of the main factors implicated in the lack of preexisting tumor T cell infiltration is crucial for the development of adapted algorithms of treatments for cold tumors.
640 citations
Journal Article•
TL;DR: The results suggest that the W6/32 antigenic determinant involves only amino acids of the HLA-A,B,C chain and is a product of their three dimensional configuration.
Abstract: The isolated HLA-A chain from intact 125I-HLA-A2 antigens weakly bound to W6/32 antibody in contrast to 125I-β2-microglobulin (β2m) isolated from the same preparation of HLA-A2 antigens that showed no demonstrable binding. when an excess of cold β2m was added to the isolated 125I-HLA-A2 chain, the binding to W6/32 antibody was considerably enhanced. These results suggest that the W6/32 antigenic determinant involves only amino acids of the HLA-A,B,C chain and is a product of their three dimensional configuration. Stable maintenance of this configuration appears to be dependent on the association of the HLA-A,B,C chain with β2m.
640 citations
TL;DR: Provenge is a novel immunotherapy agent that is safe and breaks tolerance to the tissue antigen PAP and preliminary evidence for clinical efficacy warrants further exploration.
Abstract: PURPOSE: Provenge (Dendreon Corp, Seattle, WA) is an immunotherapy product consisting of autologous dendritic cells loaded ex vivo with a recombinant fusion protein consisting of prostatic acid phosphatase (PAP) linked to granulocyte-macrophage colony-stimulating factor. Sequential phase I and phase II trials were performed to determine the safety and efficacy of Provenge and to assess its capacity to break immune tolerance to the normal tissue antigen PAP. PATIENTS AND METHODS: All patients had hormone-refractory prostate cancer. Dendritic-cell precursors were harvested by leukapheresis in weeks 0, 4, 8, and 24, loaded ex vivo with antigen for 2 days, and then infused intravenously over 30 minutes. Phase I patients received increasing doses of Provenge, and phase II patients received all the Provenge that could be prepared from a leukapheresis product. RESULTS: Patients tolerated treatment well. Fever, the most common adverse event, occurred after 15 infusions (14.7%). All patients developed immune respo...
639 citations
TL;DR: A consortium of 11 bacterial strains from the healthy human gut microbiota can strongly induce interferon-γ-producing CD8 T cells in the intestine, and enhance both resistance to bacterial infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models.
Abstract: There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103+ dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics. A consortium of 11 bacterial strains from the healthy human gut microbiota can strongly induce interferon-γ-producing CD8 T cells in the intestine, and enhance both resistance to bacterial infection and the therapeutic efficacy of immune checkpoint inhibitors.
638 citations