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Cited by 298Fungal Infections and StudiesMonoclonal and Polyclonal Antibodies ResearchAntifungal resistance and susceptibility

Characterization of a Murine Monoclonal Antibody to Cryptococcus neoformans Polysaccharide That Is a Candidate for Human Therapeutic Studies

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Casadevall, Arturo, Cleare, Wendy, Feldmesser, Marta, Glatman-Freedman, Aharona, Goldman, David L., Kozel, Thomas R., Lendvai, Nikoletta, Mukherjee, Jean +7 more·1998·Antimicrobial Agents and Chemotherapy
DOI 10.1128/aac.42.6.1437PMC PMC105619
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Abstract

The murine monoclonal antibody (MAb) 18B7 [immunoglobulin G1(κ)] is in preclinical development for treatment of Cryptococcus neoformans infections. In anticipation of its use in humans, we defined the serological and biological properties of MAb 18B7 in detail. Structural comparison to the related protective MAb 2H1 revealed conservation of the antigen binding site despite several amino acid differences. MAb 18B7 was shown by immunofluorescence and agglutination studies to bind to all four serotypes of C. neoformans , opsonize C. neoformans serotypes A and D, enhance human and mouse effector cell antifungal activity, and activate the complement pathway leading to deposition of complement component 3 (C3) on the cryptococcal capsule. Administration of MAb 18B7 to mice led to rapid clearance of serum cryptococcal antigen and deposition in the liver and spleen. Immunohistochemical studies revealed that MAb 18B7 bound to capsular glucuronoxylomannan in infected mouse tissues. No reactivity of MAb 18B7 with normal human, rat, or mouse tissues was detected. The results show that both the variable and constant regions of MAb 18B7 are biologically functional and support the use of this MAb in human therapeutic trials.

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Crossref · 10.1128/aac.42.6.1437

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  • 18B7 is a mouse-derived monoclonal antibody directed against glucuronoxylomannan, the primary component of the C. neoformans polysaccharide capsule.

    “A well-characterized example is 18B7, a mouse-derived monoclonal antibody directed against glucuronoxylomannan, the primary component of the C. neoformans polysaccharide capsule129”

    From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [129]

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Authors
Casadevall, A., Cleare, W., Feldmesser, M., Glatman-Freedman, A., Goldman, D. L., Kozel, T. R., Lendvai, N., Mukherjee, J., Pirofski, L.-A., Rivera, J., Rosas, A. L., Scharff, M. D., Valadon, P., Westin, K., & Zhong, Z.
Affiliations
  • <!--label omitted: 1-->Division of Infectious Diseases, Department of Medicine,1 and Departments of
  • <!--label omitted: 2-->Microbiology and Immunology,2
  • <!--label omitted: 3-->Pediatrics,3 and
  • University of Nevada, Reno (US)
  • Albert Einstein College of Medicine (US)
ORCID
Venue
Antimicrobial Agents and Chemotherapy
Publisher
American Society for Microbiology
Published
1998-06
Volume
42
Issue
6
Pages
1437-1446
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
DOI
10.1128/aac.42.6.1437
PMC
PMC105619
OpenAlex
W2062406170
Cited by
298
References
57
Citations by year
2026: 11 · 2025: 6 · 2024: 11 · 2023: 12 · 2022: 6 · 2021: 12 · 2020: 13 · 2019: 10 · 2018: 16 · 2017: 14 · 2016: 12 · 2015: 7 · 2014: 14 · 2013: 10 · 2012: 14
FWCI
8.39
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Antimicrobial Agents and Chemotherapy (publishedVersion)
  • PubMed Central (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r35ca039838-14)
  • National Cancer Institute (CA39838)
  • National Institute of General Medical Sciences (T32GM007491)
  • National Institute of Allergy and Infectious Diseases (AI13342, R01AI014209, AI133774, R01AI035370, P01AI037194, R37AI014209)
Topics
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Keywords
Cryptococcus neoformans, glucuronoxylomannan, capsular polysaccharide, opsonization, complement activation, C3 deposition, antibody binding sites, therapeutic antibodies, cryptococcosis
MeSH terms
Amino Acid Sequence, Animals, Antibodies, Monoclonal, Antigens, Fungal, Cryptococcus neoformans, Enzyme-Linked Immunosorbent Assay, Humans, Immunoglobulin G, Immunohistochemistry, Leukocytes, Mononuclear, Macrophages, Molecular Sequence Data, Neutrophils, Phagocytosis, Polysaccharides, Sequence Alignment, Sequence Homology, Amino Acid, Mice

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