Recombinant mannan-binding lectin (MBL) for therapy

2003 ◽  
Vol 31 (4) ◽  
pp. 763-767 ◽  
Author(s):  
J.C. Jensenius ◽  
P.H. Jensen ◽  
K. McGuire ◽  
J.L. Larsen ◽  
S. Thiel
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Clinical Evidence ◽  
Human Cell Line ◽  
Innate Immune ◽  
Genetically Determined ◽  
Micro Organisms ◽  
Mannan Binding Lectin ◽  
Binding Lectin ◽  
Increased Susceptibility

Mannan-binding lectin (MBL) is a plasma protein involved in the innate immune response. It binds to a number of micro-organisms and promotes killing of these through complement activation either directly or through opsonization. Clinical evidence indicates that in a variety of situations genetically determined low MBL levels are associated with increased susceptibility to infections. Infusions of plasma-derived MBL into MBL-deficient individuals was found to be safe in preliminary trials, but we considered that sufficient production and product safety could only be achieved through synthesis of recombinant MBL. A transfected human cell line produces MBL showing the same biological activity as plasma-derived MBL, and an essentially identical profile on MS. The production has been scaled up and clinical trials will start this year.

The mannan-binding-lectin pathway of the innate immune response

2001 ◽  
Vol 13 (1) ◽  
pp. 74-78 ◽  
Author(s):  
Mihaela Gadjeva ◽  
Steffen Thiel ◽  
Jens C Jensenius
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Lectin Pathway ◽  
Mannan Binding Lectin ◽  
Binding Lectin

Mannose-binding lectin genetics: from A to Z

2008 ◽  
Vol 36 (6) ◽  
pp. 1461-1466 ◽  
Author(s):  
Peter Garred
Keyword(s):  
Epidemiological Studies ◽  
Mannose Binding Lectin ◽  
Host Cells ◽  
Lectin Pathway ◽  
Mannose Binding ◽  
The Stability ◽  
Genetically Determined ◽  
Micro Organisms ◽  
Binding Lectin

MBL (mannose-binding lectin) is primarily a liver-derived collagen-like serum protein. It binds sugar structures on micro-organisms and on dying host cells and is one of the four known mediators that initiate activation of the complement system via the lectin pathway. Common variant alleles situated both in promoter and structural regions of the human MBL gene (MBL2) influence the stability and the serum concentration of the protein. Epidemiological studies have suggested that genetically determined variations in MBL serum concentrations influence the susceptibility to and the course of different types of infectious, autoimmune, neoplastic, metabolic and cardiovascular diseases, but this is still a subject under discussion. The fact that these genetic variations are very frequent, indicates a dual role of MBL. This overview summarizes the current molecular understanding of human MBL2 genetics.

scholarly journals Mannan-binding lectin deficiency modulates the humoral immune response dependent on the genetic environment

Immunology ◽  
2009 ◽  
Vol 127 (2) ◽  
pp. 279-288 ◽  
Author(s):  
Marieta Ruseva ◽  
Martin Kolev ◽  
Frederik Dagnaes-Hansen ◽  
Soren B. Hansen ◽  
Kazue Takahashi ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Genetic Environment ◽  
Humoral Immune ◽  
Mannan Binding Lectin ◽  
Binding Lectin

scholarly journals Immunotherapeutic strategies including transplantation: eradication of disease

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 151-157 ◽  
Author(s):  
John G. Gribben ◽  
John C. Riches
Keyword(s):  
Gene Therapy ◽  
Immune Response ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cd40 Ligand ◽  
Lymphocytic Leukemia ◽  
Effect Of Treatment ◽  
Immunomodulatory Drug ◽  
Cxcr4 Antagonists ◽  
Increased Susceptibility

Abstract Although there have been recent advances with targeted therapies in chronic lymphocytic leukemia (CLL), chemoimmunotherapy remains the treatment of choice; however, this approach is not curative. A key feature of CLL is that it induces a state of immunosuppression, causing increased susceptibility to infections and failure of an antitumor immune response, often worsened by the immunosuppressive effect of treatment. Because of its improved specificity, immunotherapy potentially offers a way out of this dilemma. Allogeneic stem cell transplantation remains the only curative option, but is hampered by the toxicity of GVHD. After many years of promise but little reward, many other immunotherapeutic approaches are now in transition to the clinical setting. Clinical trials including CLL vaccines, CXCR4 antagonists, and adoptive cellular immunotherapies such as chimeric antigen receptor–modified T cells, CD40 ligand gene therapy, and the immunomodulatory drug lenalidomide are ongoing. Results to date suggest that immunotherapeutic approaches for the treatment of CLL might finally be fulfilling their promise.

scholarly journals Regulation of Innate Immune Response toCandida albicansInfections by αMβ2-Pra1p Interaction

2011 ◽  
Vol 79 (4) ◽  
pp. 1546-1558 ◽  
Author(s):  
Dmitry A. Soloviev ◽  
Samir Jawhara ◽  
William A. Fonzi
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Cell Mediated Immunity ◽  
Fungal Virulence ◽  
Opportunistic Fungal Pathogen ◽  
Organ Invasion ◽  
Increased Susceptibility

ABSTRACTCandida albicansis a common opportunistic fungal pathogen and is the leading cause of invasive fungal diseases in immunocompromised individuals. The induction of cell-mediated immunity toC. albicansis one of the main tasks of cells of the innate immune system, andin vitroevidence suggests that integrin αMβ2(CR3, Mac-1, and CD11b/CD18) is the principal leukocyte receptor involved in recognition of the fungus. Using αMβ2-KO mice and mutated strains ofC. albicansin two models of murine candidiasis, we demonstrate that neutrophils derived from mice deficient in αMβ2have a reduced ability to killC. albicansand that the deficient mice themselves exhibit increased susceptibility to fungal infection. Disruption of thePRA1gene ofC. albicans, the primary ligand for αMβ2, protects the fungus against leukocyte killingin vitroandin vivo, impedes the innate immune response to the infection, and increases fungal virulence and organ invasionin vivo. Thus, recognition of pH-regulated antigen 1 protein (Pra1p) by αMβ2plays a pivotal role in determining fungal virulence and host response and protection againstC. albicansinfection.

scholarly journals Improvements on the purification of mannan-binding lectin and demonstration of its Ca2+-independent association with a C1s-like serine protease

1996 ◽  
Vol 319 (2) ◽  
pp. 329-332 ◽  
Author(s):  
Suet Mien TAN ◽  
Maxey C. M. CHUNG ◽  
Oi Lian KON ◽  
Steffen THIEL ◽  
Szu Hee LEE ◽  
...  
Keyword(s):  
Serine Protease ◽  
Gel Filtration ◽  
Classical Pathway ◽  
Form Analysis ◽  
Independent Association ◽  
Elution Method ◽  
Micro Organisms ◽  
Mannan Binding Lectin ◽  
Sepharose 4B ◽  
Binding Lectin

Mannan-binding lectin (MBL), previously called ‘mannan-binding protein’ or MBP, is a plasma C-type lectin which, upon binding to carbohydrate structures on micro-organisms, activates the classical pathway of complement. Purification of MBL relies on its Ca2+-dependent affinity for carbohydrate, but existing methods are susceptible to contamination by anti-carbohydrate antibodies. In the present study a sequential-sugar-elution method has been developed which can achieve a preparation of virtually pure MBL and its associated serine protease (MBL-associated serine protease, MASP) by two steps of affinity chromatography. In further separation of MASP from MBL, it was found that activated MASP was associated with MBL independent of Ca2+. Since MBL was found to bind to underivatized Sepharose 4B, the MBL-MASP complex was purified using Sepharose 4B and protease inhibitors were included to purify the complex with MASP in its proenzyme form. Analysis of thus-purified MBL-MASP complex by gel filtration on a Sephacryl S-300 column at pH 7.8 showed that the proenzyme MASP was also associated with MBL independently of Ca2+, but that the complex could be disrupted at a low pH (5.0). Therefore the mechanism of MBL-MASP-mediated complement activation appears to be significantly different from the C1-mediated classical pathway.

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