Adjunctive Immune Therapy for Fungal Infections

Casadevall, Arturo; Pirofski, Liise-anne

doi:10.1086/322710

Cited by 83 publications

(48 citation statements)

References 114 publications

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“…Hence, it is conceivable that this population may benefit most from passive therapy with specific mAb to Hc. Combination of a mAb with antifungal therapy is currently being stud-ied in a clinical trial for treatment of cryptococcosis in patients with AIDS (16), and combined therapy is considered by several mycology experts to be a valid approach to improving current antifungal regimens (65,66). Since amphotericin B is usually used for initial treatment of histoplasmosis, the addition of mAb to therapy should be considered in future studies.…”

Section: Discussionmentioning

confidence: 99%

Antibodies to a cell surface histone-like protein protect against Histoplasma capsulatum

Nosanchuk¹,

Steenbergen²,

Li³

et al. 2003

J. Clin. Invest.

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A protective role for antibodies has not previously been described for host defense against the pathogenic fungus Histoplasma capsulatum (Hc). Mouse mAb's were generated from mice immunized with Hc yeast that binds the cell surface of Hc. Administration of mAb's before Hc infection reduced fungal burden, decreased pulmonary inflammation, and prolonged survival in a murine infection model. Protection mediated by mAb's was associated with enhanced levels of IL-4, IL-6, and IFN-γ in the lungs of infected mice. The mAb's increased phagocytosis of yeast by J774.16 cells through a CR3-dependent process. Ingestion of mAb-opsonized Hc by J774.16 macrophage-like cells was associated with yeast cell growth inhibition and killing. The mAb's bound to a 17-kDa antigen expressed on the surface of Hc. The antigen was identified as a histone H2B-like protein. This study establishes that mAb's to a cell surface protein of Hc alter the intracellular fate of the fungus and mediate protection in a murine model of lethal histoplasmosis, and it suggests a new candidate antigen for vaccine development.

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Section: Discussionmentioning

confidence: 99%

Antibodies to a cell surface histone-like protein protect against Histoplasma capsulatum

Nosanchuk¹,

Steenbergen²,

Li³

et al. 2003

J. Clin. Invest.

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“…Se ha ensayado el uso de factores estimulantes de colonias, basado en que neutrófilos tratados con estos factores han mostrado in vitro mayor actividad contra Aspergillus, Candida y Mucor, por mejoría del estallido respiratorio 46,47 .…”

Section: Tratamiento De La Enfermedad De Baseunclassified

Mucormicosis en Pediatría

P¹,

2004

Rev. chil. infectol.

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IntroducciónTambién llamada phycomicosis o zigomicosis, (aunque este segundo término es más amplio y engloba además a infecciones causadas por Entomophtorales), es una afección causada por hongos saprófítos aeróbicos, generalmente no pató-genos para el hospedero inmunocompetente 1,2 . El desarrollo de enfermedad depende del estado inmune del huésped; los macrófagos y neutrófilos parecen ser el componente primario de la respuesta inmune contra estos microorganismos, previniendo la germinación de las esporas inhaladas 3 . El sello de la mucormicosis es la invasión vascular por hifas que conduce a la trombosis arterial, infarto secundario, trombosis venosa y hemorragia consecuente. Las razones de la afinidad del hongo por el tejido vascular son desconocidas y materia de especulación 2,5 . Los hongos del Orden Mucorales son microorganismos no fastidiosos que crecen en un rango de temperatura de 25 a 55° C, aeróbicos y demoran 2 a 5 días en formar colonias visibles a ojo desnudo. Las colonias tienen aspecto lanudo, a menudo parecen tenues puntos negros. Las especies de estos géneros desarrollan estolones, rizoides (en Rhizopus, Absidia y Rhizomucor) y el esporangio contiene en su extremo miriadas de esporangiosporas de 3-6 mm de diámetro cada una, que sirven como la forma de diseminación al medioambiente. La observación directa del tejido extraído, tratado con KOH al 10%, permite apreciar formas irregulares, hifas características largas y con ancho de 10 a 30 mµ, no septadas, que adoptan a menudo formas curvas o de cintas ramificadas en ángulo recto ( Etiología Mucormycosis in PediatricsMucormycosis is an infrequent infection caused by opportunistic fungi belonging to the Mucorales order; Mucoraceae family, whose characteristics are vascular invasion by hyphae, which determine thrombosis and tissue infarction. In generally affects patients with underlying diseases and produces serious invasive and often fulminant infections. Some of the risk factors leading to mucormycosis are diabetic ketoacidosis, immunosuppressive therapy, leukemia and lymphomas with prolonged neutropenia. Various clinical presentations are described, relating to anatomical site involved, being the rhinocerebral site, the most frequent one, specially in diabetic patients. Although this infection has a high morbidity and mortality, its prognosis has improved the last years, relating to therapeutic measures like correction of predisposing conditions, use of amphotericin B and early aggressive surgery. It is very important to suspect this infection in patients with predisposing conditions so an early diagnosis can be made.

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“…Furthermore, in contrast to tumor cells, yeast cells are antigenically very different from host tissue, and thus provide the potential for abundant antigen-antibody interactions with the fungal cell and low crossreaction with the host tissue. Targeting fungi with radioimmunotherapy (RIT) makes sense, because fungal diseases are notoriously difficult to treat and currently constitute a major clinical problem (8). Despite its theoretical promise, we are not aware of attempts to explore the potential usefulness of RIT against infectious diseases.…”

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Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection

Dadachova

Nakouzi

Bryan³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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115

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There is an urgent need for new antimicrobial therapies to combat drug resistance, new pathogens, and the relative inefficacy of current therapy in compromised hosts. Ionizing radiation can kill microorganisms quickly and efficiently, but this modality has not been exploited as a therapeutic antimicrobial strategy. We have developed methods to target ionizing radiation to a fungal cell by labeling a specific mAb with the therapeutic radioisotopes Rhenium-188 and Bismuth-213. Radiolabeled antibody killed cells of human pathogenic fungus Cryptococcus neoformans in vitro, thus converting an antibody with no inherent antifungal activity into a microbicidal molecule. Administration of radiolabeled antibody to mice with C. neoformans infection delivered 213 Bi and 188 Re to the sites of infection, reduced their organ fungal burden, and significantly prolonged their survival without apparent toxicity. This study establishes the principle that targeted radiation can be used for the therapy of an infectious disease, and suggests that it may have wide applicability as an antimicrobial strategy.

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Adjunctive Immune Therapy for Fungal Infections

Cited by 83 publications

References 114 publications

Antibodies to a cell surface histone-like protein protect against Histoplasma capsulatum

Antibodies to a cell surface histone-like protein protect against Histoplasma capsulatum

Mucormicosis en Pediatría

Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection

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