Abstract：
:CD3-specific antibodies have shown clinical efficacy in both transplantation and autoimmunity. However, targeting CD3 in this way can lead to T-cell activation and a serious cytokine release syndrome mediated by Fcγ receptor binding. An in vivo mouse model has been developed using severe combined immunodeficient (SCID) mice to detect human T-cell depletion and cytokine release into the circulation after administration of OKT3. This system has been used to evaluate OKT3 antibody fragments lacking the entire Fc region alongside whole antibody constructs. These data clearly show that cytokine release is detected with all OKT3 antibody constructs and fragments tested and these can be ranked from highest to lowest as follows: mIgG2a>hIgG1 (Ala-Ala)>hIgG1 diFab' maleimide (DFM)>hIgG1 F(ab')₂>mIgG2a F(ab')₂>hIgG1 Fab'. Furthermore, the monovalent hIgG1 Fab' fragment gives the least cytokine release but it does not deplete human T-cells in this assay format. This suggests that T-cell activation may be playing a role in the mechanism of action of anti-CD3 antibodies and consequently the unwanted cytokine release is potentially unavoidable for this class of molecules. This model system provides a useful tool to aid in understanding and reducing the potential risks of cytokine release following antibody therapy.
journal_name
J Immunol Methodsjournal_title
Journal of immunological methodsauthors
Malcolm SL,Smith EL,Bourne T,Shaw Sdoi
10.1016/j.jim.2012.07.001subject
Has Abstractpub_date
2012-10-31 00:00:00pages
33-42issue
1-2eissn
0022-1759issn
1872-7905pii
S0022-1759(12)00195-0journal_volume
384pub_type
杂志文章abstract：:The apoptotic process occurs asynchronically in most cell populations and its duration is variable. Therefore, the ability to continuously monitor the death process occurring in individual blood cells before, during and following apoptosis induction is crucial in the evaluation of the efficiency of pro- or anti-apopto...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/s0022-1759(03)00263-1
更新日期：2003-10-01 00:00:00
abstract：:We have developed and characterised a variant of the human T-cell tumour, MOLT-4F, which is resistant to both 8-azaguanine and 6-thioguanine. This new cell line, M4HS2, is suitable for the efficient production of lymphokine-secreting human T-cell hybrids and is available for distribution. ...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(86)90383-2
更新日期：1986-06-10 00:00:00
abstract：:A simple, rapid and reproducible method is presented for direct determination of the substitution ratio of a carrier protein with a synthetic nonradioactively labeled peptide. The peptide was covalently linked by a thiol group of a cysteine residue to the immunogenic carrier protein using the heterobifunctional reagen...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(88)90421-8
更新日期：1988-04-06 00:00:00
abstract：:External proficiency testing programs designed to evaluate the performance of end-point laboratories involved in vaccine and therapeutic clinical trials form an important part of clinical trial quality assurance. Good clinical laboratory practice (GCLP) guidelines recommend both assay validation and proficiency testin...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/j.jim.2014.05.019
更新日期：2014-07-01 00:00:00
abstract：:The major histocompatibility complex (MHC) class I related receptor, the neonatal Fc receptor (FcRn), rescues immunoglobulin G (IgG) and albumin from lysosomal degradation by recycling in endothelial cells. FcRn also contributes to passive immunity by mediating transport of IgG from mother to fetus (human) or newborn ...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/j.jim.2007.11.003
更新日期：2008-02-29 00:00:00
abstract：:A rapid antibody purification method is described which combines high performance liquid chromatography (HPLC) resolution with affinity chromatography specificity. The antigen used as immobilized ligand is bound to the HPLC column matrix by reacting the amino groups of the protein with the active epoxy groups of the l...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(88)90171-8
更新日期：1988-11-10 00:00:00
abstract：:We describe a rapid procedure for immunofluorescent screening of hybridoma supernatants. Use of primary cell cultures as substrates allows immediate detection and partial characterization of antibodies binding selectively to specific cell types. Sulfonated tissue culture cluster lids are used as a single substrate upo...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(84)90394-6
更新日期：1984-05-11 00:00:00
abstract：:The influence of various methodological variables on the CrCl3 technique for coupling antigen to the surface of erythrocytes has been investigated. Tests should be performed in protein- and phosphate-free medium. The CrCl3 stock solution should be stored at a pH of 5.0 and working dilultions prepared in acetate buffer...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(77)90198-3
更新日期：1977-01-01 00:00:00
abstract：:AMPKalpha is a subunit of AMP-activated protein kinase (AMPK), a heterotrimeric enzyme that works as a fuel sensor activated in response to the depletion of cellular ATP. AMPKalpha is considered as a master switch in regulating glucose and lipid metabolism. Determining its presence in patient sera may help in diagnosi...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/j.jim.2009.10.001
更新日期：2009-12-31 00:00:00
abstract：:A solid-phase chemiluminescence immunoassay for determining immunoglobulin G (IgG) in eluates of psoriatic scales is described. Polystyrene balls coated with protein A bound the IgG present in the eluates and in human sera. The bound IgG was then detected by a luminol-coupled goat anti-human IgG conjugate, characteriz...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(84)90184-4
更新日期：1984-05-25 00:00:00
abstract：:Dispase-treated murine hybridoma cells (SP2/0-Ag14) were transfected with the G418 resistance gene bearing plasmid pSV2-neo by electropermeabilization with a high degree of efficiency. The cells were subjected to intermittent multiple high-voltage short duration (5 microsecond) DC pulses at intervals of 1 min in a wea...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(88)90452-8
更新日期：1988-04-22 00:00:00
abstract：:We describe the use of 7-amino-actinomycin D (7AAD) to measure phagocytosis and the opsonizing capacity of serum. Heat-inactivated Candida albicans was previously stained with 7AAD and incubated with resident peritoneal macrophages. The samples were analyzed by flow cytometry and phagocytic cells were identified by th...
journal_title：Journal of immunological methods
pub_type：
doi：10.1016/s0022-1759(01)00358-1
更新日期：2001-07-01 00:00:00
abstract：:The purpose of this study was to compare and contrast two enzyme immunoassay systems: the enzyme-linked immunosorbent assay (ELISA), which utilizes polystyrene microtiter plates as the adsorptive surface and the enzyme-linked immunoflow assay (ELIFA), which utilizes nitrocellulose membranes. The principal parameter un...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(91)90152-6
更新日期：1991-08-09 00:00:00
abstract：:Rabbit immunoglobulin G (RIgG) was reduced with dithioerythritol and analyzed by high performance liquid chromatography. A quantitative method for determining the percentage of reduced half-molecules in the mixture was developed. An acetic acid concentration-dependent rate of dissociation of reduced half-molecules was...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(87)90314-0
更新日期：1987-02-11 00:00:00
abstract：:A simple and reproducible technique for murine platelet isolation is described. Such preparations then become useful in determining in vitro platelet secretory responses and platelet aggregation. ...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(80)90226-4
更新日期：1980-01-01 00:00:00
abstract：:A commonly employed method to determine the function of a particular cell population and to assess its contribution to the overall system in vivo is to selectively deplete that population and observe the effects. Using monoclonal antibodies to deliver toxins to target cells can achieve this with a high degree of effic...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/j.jim.2020.112794
更新日期：2020-08-01 00:00:00
abstract：:The reactivity of monoclonal antibodies (Mabs) raised against a cyclic peptide representing a chimeric V3 loop of HIV-1 gp120 with different peptide analogues was studied with a biosensor system (BIAcore) and by ELISA. In both assays, the Mabs cross-reacted extensively with the V3 regions of different HIV-1 strains an...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(94)90316-6
更新日期：1994-12-02 00:00:00
abstract：OBJECTIVE:The objective of this study was the identification of the stain HIF-alpha using the Image Cytometry, and to help to count the positive cells (with HIF-alpha) and the negative cells (without HIF-alpha) from the same sample. METHOD:17 images of renal tissues from male rats of Winstar lineage; overall, there we...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/j.jim.2017.02.005
更新日期：2017-05-01 00:00:00
abstract：:Malaria imposes a horrific public health burden - hundreds of millions of infections and millions of deaths - on large parts of the world. While this unacceptable health burden and its economic and social impact have made it a focal point of the international development agenda, it became consensual that malaria contr...
journal_title：Journal of immunological methods
pub_type： 杂志文章,评审
doi：10.1016/j.jim.2014.05.001
更新日期：2014-08-01 00:00:00
abstract：:Single chain antibody fragment genes are commonly created by splicing together the immunoglobulin light chain (VL) and heavy chain variable (VH) genes of a monoclonal antibody produced by a hybridoma. Selective PCR amplification of the functional immunoglobulin variable gene rearrangements can be complicated by the ex...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/j.jim.2008.04.014
更新日期：2008-07-31 00:00:00
abstract：:Murine B16 melanoma cells and metastasis variants of this tumor are resistant to NK activity mediated by normal splenocytes. The B16 cells are, however, sensitive to splenocyte-mediated cytostasis. Cytostasis was measured by a [125I]UDR incorporation-inhibition [(125I]UDR I-I) assay. The main characteristics of the [1...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(81)90066-1
更新日期：1981-01-01 00:00:00
abstract：:We describe here a specific and sensitive assay for biologically active bovine type-I interferon (IFN) in an Mx/CAT reporter gene assay. The assay is based on Madin-Darby Bovine Kidney cells transfected with a plasmid, containing a human MxA promoter driving a chloramphenicol acetyltransferase (CAT) cDNA. CAT expressi...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/s0022-1759(00)00359-8
更新日期：2001-03-01 00:00:00
abstract：:The usefulness of cryopreserved sheep erythrocytes (unsensitized or coated with fluorescein, IgG-type antibody or complement) for marker tests on human blood lymphocytes was studied. It appears that the rosetting properties or freshly prepared or frozen-stored erythrocytes are not significantly different. The method m...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(76)90118-6
更新日期：1976-01-01 00:00:00
abstract：:Delineation of the immune correlates of protection in natural infection or after vaccination is a mandatory step for vaccine development. Although the most recent techniques allow a sensitive and specific detection of the cellular immune response, a consensus on the best strategy to assess their magnitude and breadth ...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/j.jim.2011.09.005
更新日期：2012-01-31 00:00:00
abstract：:One major obstacle in antibody production is the lack of highly purified immunogen. In this study, we describe an alternative strategy to circumvent this problem. A nucleotide sequence encoding a full-length of human survivin was cloned into pAK400cb. After transforming into an E. coli Origami B strain, survivin-bioti...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/j.jim.2006.07.024
更新日期：2006-12-20 00:00:00
abstract：:Targeting of antibodies has found a number of applications in assays, anti-idiotypic therapies and vaccine design with a number of anti-idiotypic Abs generated and used in clinical applications, and some currently in clinical trials. Meanwhile, aptamers are a novel and particularly interesting targeting modality, with...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/j.jim.2004.10.011
更新日期：2005-01-01 00:00:00
abstract：:We have developed specific immunoassays for secretory peroxidase (SP) and for myeloperoxidase (MP) (polymorphonuclear leukocyte-derived peroxidase) in human saliva. Antibodies against SP and MP were produced using bovine milk lactoperoxidase (LP) and human MP as the immunogens, respectively. The methods developed are ...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(91)90154-8
更新日期：1991-08-09 00:00:00
abstract：:We developed two sensitive methods for identifying antimicrobial molecules in leukocytes and other tissues. One method uses a gel overlay technique and was designed to identify antimicrobial polypeptides in samples subjected to polyacrylamide gel electrophoresis. The other, a radial diffusion assay, allows multiple fr...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(91)90021-7
更新日期：1991-03-21 00:00:00
abstract：:Antisera used in immunological assay systems for small molecular weight substances are routinely prepared by coupling the hapten to a carrier protein via a chemical linker. Often this bridge is partly recognized by the antibody, resulting in reduced sensitivity when an identically structured tracer (e.g. iodine-labell...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(84)90296-5
更新日期：1984-11-30 00:00:00
abstract：:We describe a stable chelating linkage for the reversible immobilization of oligohistidine tagged proteins in the flow cell of the 'BIAcore' surface plasmon resonance (SPR) biosensor. The carboxymethylated dextran surface of the flow cell was covalently derivatized with N-(5-amino-1-carboxypentyl)iminodiacetic acid (N...
journal_title：Journal of immunological methods
pub_type： 杂志文章
doi：10.1016/0022-1759(95)00032-6
更新日期：1995-06-14 00:00:00
