United Kingdom (UK)
Recombinant monoclonal antibody to Melanin. Manufactured using AbAb’s Recombinant Platform with variable regions (i.e. specificity) from the hybridoma 6D2.
Alternative Name(s) of Target: CHEBI:89634
Immunogen: The original antibody was generated by immunizing 5-8 weeks old female BALB/c mice intraperitoneally with L-dopa melanin ghosts suspended in a 1:1 (vol/vol) emulsion of complete Freund's adjuvant. Digestion of in vitro-melanized C. neoformans cells with proteases, denaturant, and hot concentrated acid yields melanin particles that retain the shape of fungal cells and are therefore called melanin ghosts.
Specificity: This antibody binds melanin. Melanin is a natural pigment found in most organisms is produced in a specialized group of cells called the melanocytes.
Application Notes: Cryptococcus neoformans is an encapsulated fungus that causes life-threatening meningoencephalitis, predominantly in immunocompromised individuals. C. neoformans has a laccase (CNLAC1) that catalyzes the synthesis of polymerized melanin in vitro when the cells are grown in the presence of phenolic substrates, such as 3,4-dihydroxyphenylalanine (L-dopa). The ability of Cryptococcus neoformans to synthesize polymerized melanin in vitro has been associated with virulence. The binding characterization of this antibody towards L-dopa melanin, synthetic melanin and melanin from Sepia officinalis was carried out using ELISA. The original mouse antibody was also used for the immunofluorescence stainings of lung and brain tissues from Mel+ or Mel− C. neoformans-infected rodents (PMID: 10768981). It was reported that if the ionic strength of the solvent was increased by adding NaCl there was reduction in the binding of antibody 6D2 to melanin. IF analyses of C. neoformans-infected BALB/c mouse brain tissues suggested that 6D2 binds cell wall associated melanin (PMID: 11033020). This antibody was also reported to be used in the targeted delivery of cytotoxic radiation to human melanoma cells in vivo using 6D2 labelled with 1.5 mCi of the β-emitter 188-Rhenium (PMID: 15469923). Passive immunization with antibody to melanin like 6D2 have protective efficacy against C. neoformans infections in mice (PMID: 11292764). The safety and efficacy of 188Re-6D2 was checked in patients with metastatic melanoma and it was found that 188Re-6D2 was well tolerated, localized in melanoma metastases, and had antitumor activity (PMID: 23365757). In metastatic melanoma tumor-bearing mice, 6D2 mAb mediated complement-dependent cytotoxicity, resulting in killing of the tumor cells and suppression of tumor growth (PMID: 23557419).
Antibody first published in:
Rosas et al. Synthesis of polymerized melanin by Cryptococcus neoformans in infected rodents. Infect Immun. 2000 May; 68(5): 2845–2853. PMID:10768981
Note on publication:
Antibodies against Cryptococcus neoformans melanin were generated to be used in immunohistochemical studies of C. neoformans-infected rodents and to identify whether the fungus synthesizes polymerized melanin during the infection.