Characterization of a murine monoclonal antibody to Cryptococcus neoformans polysaccharide that is a candidate for human therapeutic studies

Arturo Casadevall, Wendy Cleare, Marta Feldmesser, Aharona Glatman-Freedman, David L. Goldman, Thomas R. Kozel, Nikoletta Lendvai, Jean Mukherjee, Liise Anne Pirofski, Johanna Rivera, Angel L. Rosas, Matthew D. Scharff, Philippe Valadon, Katherine Westin, Zhaojing Zhong

Research output: Contribution to journalArticle

Abstract

The murine monoclonal antibody (MAb) 18B7 [immunoglobulin G1(K)] 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.

Original languageEnglish (US)
Pages (from-to)1437-1446
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume42
Issue number6
StatePublished - Jun 1998
Externally publishedYes

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Cryptococcus neoformans
Polysaccharides
Monoclonal Antibodies
Therapeutics
Antigens
Complement C3
Agglutination
Capsules
Fluorescent Antibody Technique
Immunoglobulins
Spleen
Binding Sites
Amino Acids
Liver

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Characterization of a murine monoclonal antibody to Cryptococcus neoformans polysaccharide that is a candidate for human therapeutic studies. / Casadevall, Arturo; Cleare, Wendy; Feldmesser, Marta; Glatman-Freedman, Aharona; Goldman, David L.; Kozel, Thomas R.; Lendvai, Nikoletta; Mukherjee, Jean; Pirofski, Liise Anne; Rivera, Johanna; Rosas, Angel L.; Scharff, Matthew D.; Valadon, Philippe; Westin, Katherine; Zhong, Zhaojing.

In: Antimicrobial Agents and Chemotherapy, Vol. 42, No. 6, 06.1998, p. 1437-1446.

Research output: Contribution to journalArticle

Casadevall, A, Cleare, W, Feldmesser, M, Glatman-Freedman, A, Goldman, DL, Kozel, TR, Lendvai, N, Mukherjee, J, Pirofski, LA, Rivera, J, Rosas, AL, Scharff, MD, Valadon, P, Westin, K & Zhong, Z 1998, 'Characterization of a murine monoclonal antibody to Cryptococcus neoformans polysaccharide that is a candidate for human therapeutic studies', Antimicrobial Agents and Chemotherapy, vol. 42, no. 6, pp. 1437-1446.
Casadevall, Arturo ; Cleare, Wendy ; Feldmesser, Marta ; Glatman-Freedman, Aharona ; Goldman, David L. ; Kozel, Thomas R. ; Lendvai, Nikoletta ; Mukherjee, Jean ; Pirofski, Liise Anne ; Rivera, Johanna ; Rosas, Angel L. ; Scharff, Matthew D. ; Valadon, Philippe ; Westin, Katherine ; Zhong, Zhaojing. / Characterization of a murine monoclonal antibody to Cryptococcus neoformans polysaccharide that is a candidate for human therapeutic studies. In: Antimicrobial Agents and Chemotherapy. 1998 ; Vol. 42, No. 6. pp. 1437-1446.
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