Isolation and characterization of a recombinant heat shock protein of

Kumar, Anoopa; Reddy, L. J.; Sochanik, Aleksander; Kurup, Viswanath P.

doi:10.1016/0091-6749(93)90215-2

Cited by 81 publications

(39 citation statements)

References 32 publications

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“…allergen.org). Most of the identified allergens elicit humoral immune responses [26][27][28][29], others are toxic to PBMC or are strongly homologous to human proteins, while some appear to prime primarily a Th2 T cell response [30][31][32][33]. Two allergens have been shown to stimulate both T and B cell responses from patients with ABPA, Asp f2 and Asp f16 [34,35].…”

Section: I I Introductionmentioning

confidence: 99%

Generation of Th1 T cell responses directed to a HLA Class II restricted epitope from theAspergillusf16 allergen

Ramadan

Davies

Kurup

et al. 2004

Clinical and Experimental Immunology

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Section: I I Introductionmentioning

confidence: 99%

Generation of Th1 T cell responses directed to a HLA Class II restricted epitope from theAspergillusf16 allergen

Ramadan

Davies

Kurup

et al. 2004

Clinical and Experimental Immunology

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“…Different compounds have been implicated in the pathogenicity of Aspergillus fumigatus (1,2,3,6,7,10,13,14,19), but the presence of elastase activity has been considered particularly relevant because elastin constitutes a significant proportion of total lung protein (18).…”

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confidence: 99%

Correlation between the Elastase Activity Index and Invasiveness of Clinical Isolates ofAspergillus fumigatus

et al. 2002

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We calculated an elastase activity index (EAI) by dividing the diameter of the elastin lysis halo by the fungal growth diameter. After 10 days' incubation at 37°C, all strains but one obtained from invasive aspergillosis showed an EAI > 1. Of the 18 strains obtained from colonized patients, only 4 (22.2%) had an EAI > 1, whereas neither of the strains isolated from patients with fungus ball reached this value. Overall, 44 out of the 142 strains obtained from the environment had an EAI > 1 (30.9%).

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“…Patient sera containing such an antibody, and both a mouse monoclonal antibody and human recombinant antibodies against this epitope, were therapeutically active in murine models of invasive candidiasis (40,43). Homologous epitopes have been identified in a range of fungal species: Candida parapsilosis, Torulopsis glabrata, Candida tropicalis, Candida krusei, and Aspergillus fumigatus (9,12,26,38,44,66). HSP90 plays a critical role in chaperoning cellular molecules and is essential for yeast viability (46,58).…”

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confidence: 99%

Preclinical Assessment of the Efficacy of Mycograb, a Human Recombinant Antibody against Fungal HSP90

Matthews

Rigg

Hodgetts

et al. 2003

Antimicrob Agents Chemother

208

128

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Mycograb (NeuTec Pharma plc) is a human genetically recombinant antibody against fungal heat shock protein 90 (HSP90). Antibody to HSP90 is closely associated with recovery in patients with invasive candidiasis who are receiving amphotericin B (AMB). Using in vitro assays developed for efficacy assessment of chemotherapeutic antifungal drugs, Mycograb showed activity against a wide range of yeast species (MICs against Candida albicans [fluconazole {FLC}-sensitive and FLC-resistant strains], Candida krusei, Candida tropicalis, Candida glabrata, and Candida parapsilosis, 128 to 256 g/ml). Mycograb (4 or 8 g/ml) showed synergy with AMB, the fractional inhibitory index being 0.09 to 0.31. Synergy was not evident with FLC, except for FLC-sensitive C. albicans. Murine kinetics showed that Mycograb at 2 mg/kg produced a maximum concentration of drug in serum of 4.7 g/ml, a half-life at alpha phase of 3.75 min, a half-life at beta phase of 2.34 h, and an area under the concentration-time curve from 0 to t h of 155 g ⅐ min/ml. Mycograb (2 mg/kg) alone produced significant improvement in murine candidiasis caused by each species: (i) a reduction (Scheffe's test, P < 0.05) in the mean organ colony count for the FLC-resistant strain of C. albicans (kidney, liver, and spleen), C. krusei (liver and spleen), C. glabrata (liver and spleen), C. tropicalis (kidney), and C. parapsilosis (kidney, liver, and spleen) and (ii) a statistically significant increase in the number of negative biopsy specimens (Fisher's exact test, P < 0.05) for C. glabrata (kidney), C. tropicalis (liver and spleen), and C. parapsilosis (liver). AMB (0.6 mg/kg) alone cleared the C. tropicalis infection but failed to clear infections caused by C. albicans, C. krusei, C. glabrata, or C. parapsilosis. Synergy with AMB, defined as an increase (Fisher's exact test, P < 0.05) in the number of negative biopsy specimens compared with those obtained using AMB alone, occurred with the

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Isolation and characterization of a recombinant heat shock protein of

Cited by 81 publications

References 32 publications

Generation of Th1 T cell responses directed to a HLA Class II restricted epitope from theAspergillusf16 allergen

Generation of Th1 T cell responses directed to a HLA Class II restricted epitope from theAspergillusf16 allergen

Correlation between the Elastase Activity Index and Invasiveness of Clinical Isolates ofAspergillus fumigatus

Preclinical Assessment of the Efficacy of Mycograb, a Human Recombinant Antibody against Fungal HSP90

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