Profiling of internalizing tumor-associated antigens on breast and pancreatic cancer cells by reversed genomics.
Human antibodies directed towards functionally associated tumor antigens have great potentials as adjuvant treatment in cancer therapy. Here we describe an efficient subtractive approach to select single chain Fv (scFv) antibodies, specifically binding to unknown rapidly internalizing tumor-associated antigens (TAA) on human breast and pancreatic carcinoma cell lines. After re-engineering the scFv into intact IgG molecules, these fully human antibodies displayed individual binding profiles to TAAs on breast, pancreatic, colorectal and prostate carcinomas, while showing no reactivity to lymphomas. The ability of the selected antibodies to undergo receptor-mediated internalization was verified by confocal microscopy, thus proving our strategy to provide a unique set of human antibodies, potentially useful in immunotherapy.
Fransson
Johan
J
Department of Immunotechnology, Lund University, P.O. Box 7031, SE-220 07 Lund, Sweden.
Ek
Sara
S
Ellmark
Peter
P
Söderlind
Eskil
E
Borrebaeck
Carl A K
CA
Furebring
Christina
C
D000912:Antibodies, Neoplasm / Q000235:genetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000276:immunology*; D045744:Cell Line, Tumor; D004705:Endocytosis; D015316:Genetic Therapy; D006801:Humans; D018613:Microscopy, Confocal; D010190:Pancreatic Neoplasms / Q000276:immunology*; D019151:Peptide Library; D010641:Phenotype; D015202:Protein Engineering
D000912:Antibodies, Neoplasm; D019151:Peptide Library