A parallel approach to the discovery of carrier delivery vehicles to enhance antigen immunogenicity.
As part of an ongoing effort to generate human and murine monoclonal antibodies against poorly immunogenic tumor-associated antigens we have merged the rapidly expanding disciplines of parallel polymer synthesis and controlled-release technology with immunology to produce a rapid and generic approach to improve the immunogenicity of carrier-bound antigens. The process involves three stages: An array of cross-linked hydrogel materials containing a carrier protein (at various concentrations) is prepared in parallel in one step. The array is then screened in mice to determine the most effective hydrogel at enhancing the immunogenicity of the encapsulated versus nonencapsulated carrier. Finally, the most efficient hydrogel is prepared containing the critical carrier-antigen conjugate and is used for immunization protocols. The strategy was successful for the BSA-glycoconjugate of the tumor-associated antigen GM3 analogue 4. When encapsulated within the hydrogel array member most efficient at elevating BSA immunogenicity, the BSA-4 glycoconjugate was significantly more immunogenic that when administered as a free antigen.
Delgado
Mercedes
M
Department of Chemistry, The Scripps Research Institute and The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Lee
Kyung Joo
KJ
Altobell
Lawrence
L
Spanka
Carsten
C
Wentworth
Paul
P
Janda
Kim D
KD
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D002240:Carbohydrate Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D020100:Hydrogels; D018796:Immunoconjugates / Q000737:chemistry / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000276:immunology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D002352:Carrier Proteins; D020100:Hydrogels; D018796:Immunoconjugates; D007074:Immunoglobulin G; D012710:Serum Albumin, Bovine