Mycobactericidal Activity of Human Natural, Monoclonal, and Recombinant Yeast Killer Toxin‐like Antibodies

Conti, Stefania; Fanti, Franco; Magliani, Walter; Gerloni, Mara; Bertolotti, Daniela; Salati, Antonella; Cassone, Antonio; Polonelli, Luciano

doi:10.1086/517815

Cited by 42 publications

(52 citation statements)

References 11 publications

(1 reference statement)

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“…These Abs functionally mimic the cytotoxic action of the P. anomala KT, which has wide-spectrum antimicrobial activity against prokaryotic and eukaryotic microorganisms presenting receptors for KT (38). Similar activities were observed with KT-mAb and its recombinant KT-scFv (3,(35)(36)(37)39). These studies provide strong evidence that Abs can directly destroy the target organisms without the assistance of complement and immune cells.…”

supporting

confidence: 52%

“…C7, an IgM mAb raised against cell wall mannoprotein of Candida albicans, was shown to exert fungicidal effects against C. albicans by three different mechanisms: interference with adherence, inhibition of germination, and direct fungicidal activity (5); this mAb was also protective in a murine model of systemic candidosis (34). A subset of killer toxin-like Abs (KT-Abs), produced by idiotypic vaccination with mAb KT4 that was raised to neutralize a KT produced by Pichia anomala, showed broad antimicrobial activities in vitro against pathogenic bacteria, protozoa, and fungi (3,35) and provided protection in experimental models of local and systemic fungal infections (36,37). These Abs functionally mimic the cytotoxic action of the P. anomala KT, which has wide-spectrum antimicrobial activity against prokaryotic and eukaryotic microorganisms presenting receptors for KT (38).…”

mentioning

confidence: 99%

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Antibody-Dependent Cell-Mediated Cytotoxicity- and Complement-Dependent Cytotoxicity-Independent Bactericidal Activity of an IgG against Pseudomonas aeruginosa O6ad

Xie

McLean

Hall

2010

The Journal of Immunology

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supporting

confidence: 52%

mentioning

confidence: 99%

Antibody-Dependent Cell-Mediated Cytotoxicity- and Complement-Dependent Cytotoxicity-Independent Bactericidal Activity of an IgG against Pseudomonas aeruginosa O6ad

Xie

McLean

Hall

2010

The Journal of Immunology

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“…Natural yeast KT-like microbicidal antiidiotypic antibodies have been detected in both clinical and experimental settings (8,11,29). Polyclonal antibodies, MAbs, or single-chain recombinant killer antibodies appear to have fungicidal activity in vitro and to confer active and passive protection in vivo against experimental candidiasis or pneumocystosis (6,22,31,39).…”

Section: Discussionmentioning

confidence: 99%

Protection of Killer Antiidiotypic Antibodies against Early Invasive Aspergillosis in a Murine Model of Allogeneic T-Cell-Depleted Bone Marrow Transplantation

Cenci¹,

Mencacci²,

Spreca

et al. 2002

Infect Immun

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Antiidiotypic monoclonal antibodies (MAbs) representing the internal image of a yeast killer toxin (KT)have therapeutic potential against several fungal infections. The efficacy of KT MAbs against Aspergillus fumigatus was investigated in a mouse model of T-cell-depleted allogeneic bone marrow transplantation (BMT) with invasive pulmonary aspergillosis. Mice were highly susceptible to infection at 3 days post-BMT, when profound neutropenia was observed both in the periphery and in the lungs. Treatment with KT MAbs protected the mice from infection, as judged by the long-term survival and decreased pathology associated with inhibition of fungal growth and hyphal development in the lungs. In vitro, similar to polymorphonuclear neutrophils, KT MAbs significantly inhibited the hyphal development and metabolic activity of germinated Aspergillus conidia. These results indicate that mimicking the action of neutrophils could be a strategy through which KT MAbs exert therapeutic efficacy in A. fumigatus infections.Invasive fungal infections remain a major problem for bone marrow (BM) transplant (BMT) recipients (35,45). Mortality from opportunistic fungal infections exceeds 50% in most studies and has been reported to be as high as 95% in allogeneic BMT recipients with Aspergillus sp. infection, despite aggressive antifungal therapy (4).Studies in vitro and in animal models have indicated that the innate defenses are primarily responsible for the elimination of inhaled conidia from the lungs (10,13,19,38). Early fungal clearance is mediated by a dual phagocytic system involving both alveolar macrophages and recruited polymorphonuclear leukocytes capable of efficiently opposing fungal infectivity at the level of conidia or hyphal forms (37). However, the killing of phagocytosed conidia by mononuclear cells is a slow process that occurs with a low killing rate and depends on the immunocompetence of effector monocytes (19). Moreover, the finding that the conidiocidal activity of monocytes in both clinical disease and experimental chronic granulomatous disease is largely unaffected (26) reveals the unique importance of neutrophil activity against germinating conidia and hyphae in the control of aspergillosis.Human studies have shown that prolonged neutropenia is one of the most important factors predisposing to invasive aspergillosis (35,45). However, the efficacy of immunotherapies aimed at both shortening the duration of neutropenia and restoring neutrophil antifungal activity has been limited by problems associated with the transfusion therapy, including the still uncertain efficacy of colony-stimulating factors (34) and the limited persistence of the transfused cells (16). It appears that strategies aimed at keeping the infection in check until the recovery of adequate innate antifungal activity are needed for prompt handling of the fungus by the host.Recent studies have highlighted the therapeutic potential of killer antiidiotypic antibodies in several fungal infections (23). Antiidiotypes to a monoclonal antibody (MAb)...

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“…In addition, great difficulty was encountered by investigators trying to demonstrate natural protective Ab responses to M. tuberculosis (reviewed in references 27 and 28). However, in recent years, studies from several laboratories used monoclonal Abs (MAbs) to demonstrate beneficial effects of Abs on various aspects of M. tuberculosis infection (11,17,30,57,76,80).…”

mentioning

confidence: 99%

Do CD1-Restricted T Cells Contribute to Antibody-Mediated Immunity againstMycobacterium tuberculosis?

Lang¹,

Glatman‐Freedman

2006

Infect Immun

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Mycobactericidal Activity of Human Natural, Monoclonal, and Recombinant Yeast Killer Toxin‐like Antibodies

Cited by 42 publications

References 11 publications

Antibody-Dependent Cell-Mediated Cytotoxicity- and Complement-Dependent Cytotoxicity-Independent Bactericidal Activity of an IgG against Pseudomonas aeruginosa O6ad

Antibody-Dependent Cell-Mediated Cytotoxicity- and Complement-Dependent Cytotoxicity-Independent Bactericidal Activity of an IgG against Pseudomonas aeruginosa O6ad

Protection of Killer Antiidiotypic Antibodies against Early Invasive Aspergillosis in a Murine Model of Allogeneic T-Cell-Depleted Bone Marrow Transplantation

Do CD1-Restricted T Cells Contribute to Antibody-Mediated Immunity againstMycobacterium tuberculosis?

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