Systematic amino acid substitutions improved efficiency of GD2-peptide mimotope vaccination against neuroblastoma.
The likelihood of identifying peptides of sufficient quality for the development of effective cancer vaccines by screening of phage display libraries is low. Here, we introduce the sequential application of systematic amino acid substitution by SPOT synthesis. After the substitution of two amino acids within the sequence of a phage display-derived mimotope of disialoganglioside GD2 (mimotope MA), the novel mimotope C3 showed improved GD2 mimicry in vitro. Peptide vaccination with the C3 mimotope induced an 18-fold increased anti-GD2 serum response associated with reduction of primary tumour growth and spontaneous metastasis in contrast to MA mimotope controls in a syngeneic neuroblastoma model. In summary, SPOT provides an ideal optimisation tool for the development of phage display-derived cancer vaccines.
Bleeke
Matthias
M
Charité - Universitätsmedizin Berlin, Department of Pediatrics, Experimental Oncology, Berlin, Germany.
Fest
Stefan
S
Huebener
Nicole
N
Landgraf
Christiane
C
Schraven
Burkhart
B
Gaedicke
Gerhard
G
Volkmer
Rudolf
R
Lode
Holger N
HN
D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D005732:Gangliosides / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007110:Immunity, Active / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000378:metabolism; D051379:Mice; D018716:Molecular Mimicry / Q000235:genetics*; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000473:pathology / Q000517:prevention & control*; D040081:Protein Array Analysis / Q000379:methods
D019496:Cancer Vaccines; D005732:Gangliosides; D007074:Immunoglobulin G; C025447:sialogangliosides