Maleimide conjugation markedly enhances the immunogenicity of both human and murine idiotype-KLH vaccines.


:The collection of epitopes present within the variable regions of the tumor-specific clonal immunoglobulin expressed by B cell lymphomas (idiotype, Id) can serve as a target for active immunotherapy. Traditionally, tumor-derived Id protein is chemically conjugated to the immunogenic foreign carrier protein keyhole limpet hemocyanin (KLH) using glutaraldehyde to serve as a therapeutic vaccine. While this approach offered promising results for some patients treated in early clinical trials, glutaraldehyde Id-KLH vaccines have failed to induce immune and clinical responses in many vaccinated subjects. We recently described an alternative conjugation method employing maleimide-sulfhydryl chemistry that significantly increased the therapeutic efficacy of Id-KLH vaccines in three different murine B cell lymphoma models, with protection mediated by either CD8(+) T cells or antibodies. We now define in detail the methods and parameters critical for enhancing the in vivo immunogenicity of human as well as murine Id-KLH conjugate vaccines. Optimal conditions for Id sulfhydryl pre-reduction were determined, and maleimide Id-KLH conjugates maintained stability and potency even after prolonged storage. Field flow fractionation analysis of Id-KLH particle size revealed that maleimide conjugates were far more uniform in size than glutaraldehyde conjugates. Under increasingly stringent conditions, maleimide Id-KLH vaccines maintained superior efficacy over glutaraldehyde Id-KLH in treating established, disseminated murine lymphoma. More importantly, human maleimide Id-KLH conjugates were consistently superior to glutaraldehyde Id-KLH conjugates in inducing Id-specific antibody and T cell responses. The described methods should be easily adaptable to the production of clinical grade vaccines for human trials in B cell malignancies.


Mol Immunol


Molecular immunology


Kafi K,Betting DJ,Yamada RE,Bacica M,Steward KK,Timmerman JM




Has Abstract


2009-01-01 00:00:00














  • Humanization of a mouse anti-human interleukin-6 receptor antibody comparing two methods for selecting human framework regions.

    abstract::Mouse monoclonal antibody AUK12-20 binds to human IL-6 receptor and inhibits IL-6 functions. It has been humanized by CDR-grafting for therapeutic use. In the design of reshaped human AUK12-20 VL region, the human framework regions (FRs) from the human Bence-Jones protein REI were used. The reshaped human AUK12-20 lig...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Sato K,Tsuchiya M,Saldanha J,Koishihara Y,Ohsugi Y,Kishimoto T,Bendig MM

    更新日期:1994-04-01 00:00:00

  • Inhibition of mast cell degranulation by a chimeric toxin containing a novel phosphatidylinositol-3,4,5-triphosphate phosphatase.

    abstract::It is well established that many cell functions are controlled by the PI-3K signaling pathway and the signaling lipid, phosphatidylinositol-3,4,5-triphosphate (PIP3). This is particularly true for mast cells which play a key regulatory role in allergy and inflammation through activation via high-affinity IgE receptors...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Shenker BJ,Boesze-Battaglia K,Zekavat A,Walker L,Besack D,Ali H

    更新日期:2010-11-01 00:00:00

  • Acute arsenic exposure induces inflammatory responses and CD4+ T cell subpopulations differentiation in spleen and thymus with the involvement of MAPK, NF-kB, and Nrf2.

    abstract::Increasing lines of evidence indicate that arsenic may be associated with immune related problems, but its detailed effects on immune organs are poorly understood. The objective of this study was to explore inflammatory responses and T cell differentiation of arsenic exposure in spleen and thymus. Female C57BL/6 mice ...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Duan X,Gao S,Li J,Wu L,Zhang Y,Li W,Zhao L,Chen J,Yang S,Sun G,Li B

    更新日期:2017-01-01 00:00:00

  • Triptolide inhibits B7-H1 expression on proinflammatory factor activated renal tubular epithelial cells by decreasing NF-kappaB transcription.

    abstract::Triptolide has been used extensively in China for the treatment of autoimmune diseases and tumor for many centuries. Nevertheless, little is known about its exact immunosuppressive and anti-inflammatory properties. Increasing recognition of the importance of renal tubular epithelial cells (TECs) in renal diseases rais...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Chen Y,Zhang J,Li J,Zhao T,Zou L,Tang Y,Zhang X,Wu Y

    更新日期:2006-03-01 00:00:00

  • Toward an atomistic understanding of the immune synapse: large-scale molecular dynamics simulation of a membrane-embedded TCR-pMHC-CD4 complex.

    abstract::T-cell activation requires interaction of T-cell receptors (TCR) with peptide epitopes bound by major histocompatibility complex (MHC) proteins. This interaction occurs at a special cell-cell junction known as the immune or immunological synapse. Fluorescence microscopy has shown that the interplay among one agonist p...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Wan S,Flower DR,Coveney PV

    更新日期:2008-03-01 00:00:00

  • The mechanism of action of tapasin in the peptide exchange on MHC class I molecules determined from kinetics simulation studies.

    abstract::To understand the mechanism of action of the chaperone protein tapasin, which mediates loading of high-affinity peptides onto major histocompatibility complex (MHC) class I molecules in the antiviral immune response, we have performed numerical simulations of the class I-peptide binding process with four different mec...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Schneeweiss C,Garstka M,Smith J,Hütt MT,Springer S

    更新日期:2009-06-01 00:00:00

  • Unique biochemical properties of a mutant MHC class I molecule, H-2Ksm1.

    abstract::This study describes serological and biochemical properties of a novel MHC class I molecule. The mutant H-2Ksm1 molecule was discovered in a mouse because of loss of reactivity of its peripheral blood lymphocytes to monoclonal antibodies. This mutation in the H-2Ks molecule is the first in vivo mutation described that...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Hasenkrug KJ,Kesari KV,Nathenson SG

    更新日期:1992-12-01 00:00:00

  • Notch activation in thymic epithelial cells induces development of thymic microenvironments.

    abstract::The development and maintenance of thymic microenvironments depends on sustained crosstalk signals derived from developing thymocytes. However, the molecular basis for the initial phase in the lymphoid dependent development of thymic epithelial cells (TECs) remains unclear. Here we show that similarly to regular thymo...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Masuda K,Germeraad WT,Satoh R,Itoi M,Ikawa T,Minato N,Katsura Y,van Ewijk W,Kawamoto H

    更新日期:2009-05-01 00:00:00

  • Evidence that the hinge region plays a role in maintaining serum levels of the murine IgG1 molecule.

    abstract::The site of the murine IgG1 molecule that regulates catabolism has recently been shown to encompass amino acids that are located at the CH2-CH3 domain interface. The CH2 and CH3 domains are connected to each other by a relatively flexible "mini-hinge" region, and flexibility in this region could clearly affect the ori...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Kim JK,Tsen MF,Ghetie V,Ward ES

    更新日期:1995-05-01 00:00:00

  • Inducible overexpression of zebrafish microRNA-722 suppresses chemotaxis of human neutrophil like cells.

    abstract::Neutrophil migration is essential for battling against infections but also drives chronic inflammation. Since primary neutrophils are terminally differentiated and not genetically tractable, leukemia cells such as HL-60 are differentiated into neutrophil-like cells to study mechanisms underlying neutrophil migration. ...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Hsu AY,Liu S,Syahirah R,Brasseale KA,Wan J,Deng Q

    更新日期:2019-08-01 00:00:00

  • Deficiency of SHP1 leads to sustained and increased ERK activation in mast cells, thereby inhibiting IL-3-dependent proliferation and cell death.

    abstract::SHP-1 plays an important role for the regulation of signaling from various hematopoietic cell receptors. In this study, we examined IL-3-induced cell proliferation and IL-3 depletion-induced apoptosis in bone marrow-derived mast cells (BMMC) established from motheaten (me) that lack SHP-1 expression, viable motheaten ...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Nakata K,Suzuki Y,Inoue T,Ra C,Yakura H,Mizuno K

    更新日期:2011-01-01 00:00:00

  • Identification of an Sp factor-dependent promoter in GCET, a gene expressed at high levels in germinal center B cells.

    abstract::Antigen-stimulated B lymphocytes undergo genetic and phenotypic changes in germinal centers (GCs), including affinity maturation of immunoglobulin (Ig) genes and Ig heavy chain isotype switching. Expression of the Germinal Center Expressed Transcript (GCET) gene is up-regulated in murine GC B cells. The human homolog ...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Steinke JW,Hodsdon W,Parenti S,Ostraat R,Lutz R,Borish L,Hagman J

    更新日期:2004-11-01 00:00:00

  • An additional hypervariable region encoded by V gene segments occurs in Tcr V beta at a location compatible with its involvement in Tcr active site--a general model for alloreactivity.

    abstract::The number of V alpha and V beta sequences of T cell receptors now available allows a meaningful analysis of their variability profiles. Variability plots were derived using a modified form of Wu and Kabat's algorithm: variability is not computed as a proportion of the number of different residues occurring at a posit...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Wuilmart C,Urbain J

    更新日期:1991-09-01 00:00:00

  • Ecto-F1-ATPase and MHC-class I close association on cell membranes.

    abstract::Subunits of the mitochondrial ATP synthase complex are expressed on the surface of tumors, bind the TCR of human Vgamma9/Vdelta2 lymphocytes and promote their cytotoxicity. Present experiments show that detection of the complex (called ecto-F1-ATPase) at the cell surface by immunofluorescence correlates with low MHC-c...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Vantourout P,Martinez LO,Fabre A,Collet X,Champagne E

    更新日期:2008-01-01 00:00:00

  • Cloning and characterization of murine CD6.

    abstract::The lymphocyte antigen CD6 has been extensively studied in humans, but has not been reported in mouse. Here we describe the isolation and characterization of a cDNA clone encoding the murine homologue of the human lymphocyte antigen CD6. Comparison of the predicted amino acid sequence of human and murine CD6 shows tha...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Whitney G,Bowen M,Neubauer M,Aruffo A

    更新日期:1995-01-01 00:00:00

  • Cytohesin-1 regulates human blood neutrophil adhesion to endothelial cells through β2 integrin activation.

    abstract::Cytohesin-1 is a guanine nucleotide exchange factor for ADP ribosylation factor 6 (Arf6) in human blood neutrophils and differentiated PLB-985 neutrophil-like cells. Cytohesin-1 regulates adhesion and the transendothelial migration of monocytes, dendritic cells and T lymphocytes through activation of the β2 integrin L...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: El azreq MA,Bourgoin SG

    更新日期:2011-07-01 00:00:00

  • Atypical combined immunodeficiency due to Artemis defect: a case presenting as hyperimmunoglobulin M syndrome and with LGLL.

    abstract::SCID can be caused by various genetic mutations leading to distinctive phenotypes according to the presence of T, B and NK cells. Artemis is a gene encoded on chromosome 10p. The deficiency of this molecule causes an inability to repair DNA double strand breaks and is one of the causes of radiosensitive T-B-NK+ SCID. ...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Bajin İY,Ayvaz DÇ,Ünal S,Özgür TT,Çetin M,Gümrük F,Tezcan İ,de Villartay JP,Sanal Ö

    更新日期:2013-12-01 00:00:00

  • A novel Aβ epitope vaccine based on bacterium-like particle against Alzheimer's disease.

    abstract::Amyloid-beta (Aβ) plaque accumulation in the brain is one of the hallmarks of Alzheimer's disease (AD). Immunotherapy against Aβ was considered a potential strategy for reducing the Aβ load in the brain. However, none of the Aβ immunotherapies have produced clinically meaningful results to date, due to poor safety or ...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Fu L,Guo Y,Sun Y,Dong Y,Wu J,Yu B,Zhang H,Yu X,Wu H,Kong W

    更新日期:2018-09-01 00:00:00

  • Structure and function of major histocompatibility complex (MHC) class I specific receptors expressed on human natural killer (NK) cells.

    abstract::Natural killer (NK) cells express receptors that are specific for MHC class I molecules. These receptors play a crucial role in regulating the lytic and cytokine expression capabilities of NK cells. In humans, three distinct families of genes have been defined that encode for receptors of HLA class I molecules. The fi...

    journal_title:Molecular immunology

    pub_type: 杂志文章,评审


    authors: Borrego F,Kabat J,Kim DK,Lieto L,Maasho K,Peña J,Solana R,Coligan JE

    更新日期:2002-02-01 00:00:00

  • Binding specificity of a monoclonal anti-DNA antibody.

    abstract::To investigate the interaction of DNA and anti-DNA antibodies in the immune complex disease of systemic lupus erythematosus, the fine specificity of binding of a monoclonal anti-DNA antibody was determined. This antibody, termed Cll, was derived from the fusion of spleen cells from an autoimmune MRL-lpr/lpr mouse with...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Pisetsky DS,Caster SA

    更新日期:1982-05-01 00:00:00

  • Evidence for 65 electrophoretically distinct groups of light chains in BALB/c and NZB myelomas.

    abstract::Light chains of 426 randomly selected myelomas from BALB/c and NZB mice were characterized by isoelectric focusing (IF) and electrophoresis at pH 3. Approximately 50% of the light chains in each strain were found to have unique electrophoretic properties. The remaining 50% of light chains fell into groups of two or mo...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Gibson DM

    更新日期:1984-05-01 00:00:00

  • HLA class II allele frequencies in the Lebanese population.

    abstract::Human leukocyte antigens (HLA) allele determination is becoming an increasingly important aspect in the field of transplantation as well as in the area of HLA association with a number of diseases. Through Lebanon's history, this country, situated at a crossroads between Europe, Asia and Africa, has been a host for va...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Samaha H,Rahal EA,Abou-Jaoude M,Younes M,Dacchache J,Hakime N

    更新日期:2003-07-01 00:00:00

  • Analysis and characterization of the expression of the secretory and membrane forms of IgM heavy chains in the pufferfish, Takifugu rubripes.

    abstract::We investigated the structure and expression of immunoglobulin genes in the pufferfish, Takifugu rubripes, a highly prized and economically important fish species. The cDNA fragment that partially encodes the constant region of the IgM heavy chain was isolated in these animals by RACE using degenerate primers after wh...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Saha NR,Suetake H,Suzuki Y

    更新日期:2005-01-01 00:00:00

  • NF-kappaB family of transcription factor facilitates gene conversion in chicken B cells.

    abstract::Activation-induced cytidine deaminase (AID) is critical for immunoglobulin (Ig) diversification in B cells. The majority of evidence supports the model that AID modifies Ig genes at the DNA level by deaminating cytosines into uracils. The mutagenic activity is largely restricted to Ig genes to avoid genomic damage in ...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Kim Y,Tian M

    更新日期:2009-10-01 00:00:00

  • Effects of eosinophils on mast cells: a new pathway for the perpetuation of allergic inflammation.

    abstract::Mast cells have a clear-cut pathologic role in allergy, participating in a number of chronic inflammatory conditions, in helmintic parasitosis, and in some solid tumor reactions, but also in physiological situations, such as wound healing and innate immunity. Mast cells release a large number of proinflammatory, immun...

    journal_title:Molecular immunology

    pub_type: 杂志文章,评审


    authors: Piliponsky AM,Gleich GJ,Bar I,Levi-Schaffer F

    更新日期:2002-09-01 00:00:00

  • MiR-143-3p controls TGF-β1-induced cell proliferation and extracellular matrix production in airway smooth muscle via negative regulation of the nuclear factor of activated T cells 1.

    abstract::MicroRNAs (miRNAs) are small noncoding RNAs that function in diverse biological processes. However, little is known about the precise role of microRNAs in the functioning of airway smooth muscle cells (ASMCs). Here, we investigated the potential role and mechanisms of the miR-143 -3p on proliferation and the extracell...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Cheng W,Yan K,Xie LY,Chen F,Yu HC,Huang YX,Dang CX

    更新日期:2016-10-01 00:00:00

  • The molecular allergology of subtropical grass pollen.

    abstract::Grass pollens are amongst the most important aeroallergen sources world-wide triggering allergic rhinoconjunctivitis and asthma in sensitised patients. Much of what we know about the allergen components of grasses is informed by research on pollen of temperate (Pooideae) species that are abundant in the temperate clim...

    journal_title:Molecular immunology

    pub_type: 杂志文章,评审


    authors: Kailaivasan T,Davies JM

    更新日期:2018-08-01 00:00:00

  • Linkage of a tumor immune function and cell cycle de-regulation via a gene regulatory network subcircuit.

    abstract::Gene regulatory network (GRN) subcircuits have been described for cell fate progressions in animal development. The hallmark of these subcircuits is the integration of promoters, and positive- and negative-acting promoter binding proteins, such that an alteration in function of any one member of the defined subcircuit...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Xu L,Niesen MI,Blanck G

    更新日期:2009-02-01 00:00:00

  • T cell dependent differentiation of human B cells: direct switch from IgM to IgE, and sequential switch from IgM via IgG to IgA production.

    abstract::Ig production by splenic human B cells that express different surface Ig isotypes were analysed in limiting dilution cultures. Therefore, FACS sorted IgM+, IgG+ and IgA1+ B cells were stimulated with PMA-activated EL4 thymoma cells as helper cells in the presence of IL-2 and IL-4. We found that at least every second B...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Brinkmann V,Müller S,Heusser CH

    更新日期:1992-10-01 00:00:00

  • Major mountain cedar allergen, Jun a 1, contains conformational as well as linear IgE epitopes.

    abstract::We have previously identified four linear IgE epitopes on Jun a 1, the dominant allergen in mountain cedar pollen, and mapped these to the surfaces of a molecular model and to the crystal structure of this glycoprotein. The aim of the present study was to determine if Jun a 1 also displays conformational IgE epitopes....

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Varshney S,Goldblum RM,Kearney C,Watanabe M,Midoro-Horiuti T

    更新日期:2007-04-01 00:00:00