Dysfunctional Antibodies in the Tumor Microenvironment Associate with Impaired Anticancer Immunity.
AuthorsZhang N, Deng H, Fan X, Gonzalez A, Zhang S, Brezski RJ, Choi BK, Rycyzyn M, Strohl W, Jordan R, An Z,
Journal
PubMed ID26224871
'Studies have demonstrated that cancer-associated matrix metalloproteinases (MMP) can generate single peptide bond cleavages in the hinge region of immunoglobulin G1 (IgG1). This study investigated the cleavage of endogenous IgGs by MMPs in the tumor microenvironment and the consequences of the IgG hinge cleavage for humoral immunity. We investigated the ... More
ABO antibody and complement depletion by immunoadsorption combined with membrane filtration--a randomized, controlled, cross-over trial.
AuthorsEskandary F, Wahrmann M, Biesenbach P, Sandurkov C, König F, Schwaiger E, Perkmann T, Künig S, Derfler K, Zlabinger GJ, Böhmig GA,
Journal
PubMed ID24378525
'Potent antibody depletion techniques have paved the way to successful ABO-incompatible transplantation. Considering its efficiency regarding IgG removal, the use of non-antigen-specific semi-selective immunoadsorption (IA) has been advocated. One attractive strategy to overcome the caveat of incomplete IgM depletion and to interfere with complement activation could be the adjunctive use ... More
Broad neutralization of human immunodeficiency virus type 1 mediated by plasma antibodies against the gp41 membrane proximal external region.
'We identified three cross-neutralizing plasma samples with high-titer anti-membrane proximal external region (MPER) peptide binding antibodies from among 156 chronically human immunodeficiency virus type 1-infected individuals. In order to establish if these antibodies were directly responsible for the observed neutralization breadth, we used MPER-coated magnetic beads to deplete plasmas of ... More
Pathological crystallization of human immunoglobulins.
AuthorsWang Y, Lomakin A, Hideshima T, Laubach JP, Ogun O, Richardson PG, Munshi NC, Anderson KC, Benedek GB,
JournalProc Natl Acad Sci U S A
PubMed ID22847421
'Condensation of Igs has been observed in pharmaceutical formulations and in vivo in cases of cryoglobulinemia. We report a study of monoclonal IgG cryoglobulins overexpressed by two patients with multiple myeloma. These cryoglobulins form crystals, and we measured their solubility lines. Depending on the supersaturation, we observed a variety of ... More
Cytosolic DNA-activated human dendritic cells are potent activators of the adaptive immune response.
AuthorsKis-Toth K, Szanto A, Thai TH, Tsokos GC,
JournalJ Immunol
PubMed ID21709148
Recent studies in cell lines and genetically engineered mice have demonstrated that cytosolic dsDNA could activate dendritic cells (DCs) to become effector APCs. Recognition of DNA might be a major factor in antimicrobial immune responses against cytosolic pathogens and also in human autoimmune diseases such as systemic lupus erythematosus. However, ... More
Human monoclonal antibodies against anthrax lethal factor and protective antigen act independently to protect against Bacillus anthracis infection and enhance endogenous immunity to anthrax.
The unpredictable nature of bioterrorism and the absence of real-time detection systems have highlighted the need for an efficient postexposure therapy for Bacillus anthracis infection. One approach is passive immunization through the administration of antibodies that mitigate the biological action of anthrax toxin. We isolated and characterized two protective fully ... More
Double trans-chromosomic mice: maintenance of two individual human chromosome fragments containing Ig heavy and kappa loci and expression of fully human antibodies.
AuthorsTomizuka K, Shinohara T, Yoshida H, Uejima H, Ohguma A, Tanaka S, Sato K, Oshimura M, Ishida I,
JournalProc Natl Acad Sci U S A
PubMed ID10639146
The use of a human chromosome or its fragment as a vector for animal transgenesis may facilitate functional studies of large human genomic regions. We describe here the generation and analysis of double trans-chromosomic (Tc) mice harboring two individual human chromosome fragments (hCFs). Two transmittable hCFs, one containing the Ig ... More
Immunogenicity of a fucosyl-GM1-keyhole limpet hemocyanin conjugate vaccine in patients with small cell lung cancer.
AuthorsDickler MN, Ragupathi G, Liu NX, Musselli C, Martino DJ, Miller VA, Kris MG, Brezicka FT, Livingston PO, Grant SC
JournalClin Cancer Res
PubMed ID10537341
Although small cell lung cancer (SCLC) is highly responsive to chemotherapy, relapses are common, and most patients die within 2 years of diagnosis. After initial therapy, standard treatment is observation alone. We have been investigating immunization against selected gangliosides as adjuvant therapy directed against residual and presumably resistant disease persisting ... More