Mammalian receptors as targets for antibody and active vaccination therapy against mold infections

a technology of mammalian receptors and active vaccination therapy, which is applied in the field of compositions and methods for treating and preventing infectious diseases in patients, can solve the problems mucormycosis, and human fungal infection, and the effect of nephrotoxicity and other adverse effects, and the use of antifungal therapy alone is rarely curativ

Inactive Publication Date: 2011-03-10
LOS ANGELES BIOMEDICAL RES INST AT HARBOR UCLA MEDICAL CENT
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Benefits of technology

[0014]In another embodiment, the present invention provides methods of treating or preventing a fungal condition by administering to a subject having, or susceptible to having, a fungal condition a therapeutically effective amount of an antibody or antibody fragment thereof that specifically binds to a GRP78 polypeptide or a fragment thereof.
[0015]In another embodiment, the present invention provides methods of treating or preventing a fungal condition by administering to

Problems solved by technology

Fungi of the class Zygomycetes, order Mucorales, can cause Mucormycosis, a potentially deadly fungal infection in human.
Because the fungus is relatively resistant to AmB, high doses are required, which frequently cause nephrotoxicity and other adverse effects (Sugar, supra).
Also, in the absence of surgical removal of the infected focus (such as excision of the

Method used

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  • Mammalian receptors as targets for antibody and active vaccination therapy against mold infections
  • Mammalian receptors as targets for antibody and active vaccination therapy against mold infections
  • Mammalian receptors as targets for antibody and active vaccination therapy against mold infections

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Endothelial Cell Receptor GRP78 is Required for Mucormycosis Pathogenesis

[0122]Mucormycosis is a life-threatening infection caused by fungi of the order Mucorales, the most common etiologic species of which is Rhizopus oryzae. The most common predisposing risk factor for mucormycosis is diabetes mellitus, and it has been long established that patients with diabetic ketoacidosis (DKA) have a unique predisposition to this infection (Ibrahim et al., Clinical Mycology, Dismukes et al., eds. New York, N.Y.: Oxford University Press, pp. 241-251 (2003) Spellberg et al., Clin Microbiol Rev. 18(3):556-569 (2005)). Unfortunately, despite surgical debridement and first-line antifungal therapy, the overall mortality of mucormycosis remains unacceptably high, and survivors are typically left with considerable disfigurement from the infection and surgery (Spellberg (2005) supra; Gleissner et al., Leuk Lymphoma 45(7):1351-1360 (2004)).

[0123]A hallmark of mucormycosis is the presence of extensive a...

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Abstract

The present invention provides therapeutic compositions and methods for treating and preventing fungal disease or conditions including mucormycosis. The therapeutic methods and compositions of the invention include antibody, antibody fragment, siRNA and vaccine compositions having or directed against a GRP78 polypeptide or an antigenic fragment of the polypeptide.

Description

[0001]This application claims the benefit of priority to the U.S. provisional patent application Ser. No. 61 / 239,026, filed Sep. 1, 2009, which is herein incorporated by reference in its entirety.[0002]This invention was made in part with U.S. Government support under NIH grant 011671 awarded by NIAID. The U.S. Government can have certain rights in the invention.BACKGROUND OF THE INVENTION [0003]This invention generally relates to compositions and methods for treating and preventing infectious diseases in a patient and, more particularly, relates to compositions and methods using antibodies, antibody fragments, small interfering RNAs or vaccines for treating and preventing opportunistic fungal diseases.[0004]About 180 of the 250,000 known fungal species are recognized to cause disease (mycosis) in man and animal. Some of fungi can establish an infection in all exposed subjects, e.g., the systemic pathogens Histoplasma capsulatum and Coccidioides immitis. Others, such as Candida, Ase...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61P31/10A61K31/713A61K39/00
CPCA61K31/713A61K39/0002A61K39/0005A61K2039/505C07K16/14C07K2317/77C07K2317/76C12N2310/14C12N2310/531C12N2799/027C12N2799/06A61K39/39575C12N15/1138A61P31/10C07K16/18C07K2317/24
Inventor IBRAHIM, ASHRAF S.LIU, MINGFUSPELLBERG, BRAD J.FILLER, SCOTTFU, YUEEDWARDS, JOHN E.
Owner LOS ANGELES BIOMEDICAL RES INST AT HARBOR UCLA MEDICAL CENT
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