Cloning of B cell lymphoma-associated antigens using modified phage-displayed expression cDNA library and immunized patient sera.
Active immunization of follicular lymphoma patients with idiotypic vaccines elicits antigen-specific antibody responses, T-cell responses, and antitumor effects. We hypothesized that these vaccinated patients could generate tumor-specific immune responses, not only against idiotype, but also against other tumor-associated antigens (TAA) by a mechanism of epitope spreading. To identify potential antigens, a phage surface expressed cDNA library derived from primary tumor cells was screened with sera from idiotype-vaccinated patients. Consistent with our hypothesis, we identified two immunogenic peptides (FL-aa-7 and 18), unrelated to idiotype, which were recognized by postvaccine sera but not by prevaccine or normal human sera. These peptide sequences derived from the 5'-untranslated regions of the human GTPase, IMAP family member 7 gene (FL-aa-7) and an alternative reading frame of U1-snRNP 70 (FL-aa-18), respectively, suggesting that epitope spreading had occurred.
Cha
Soung-Chul
SC
Department of Lymphoma and Myeloma, Division of Cancer Medicine, Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0903, Houston, TX 77030, USA.
Kwak
Larry W
LW
Ruffini
Pier Adelchi
PA
Qin
Hong
H
Neelapu
Sattva
S
Biragyn
Arya
A
D000595:Amino Acid Sequence; D000912:Antibodies, Neoplasm / Q000097:blood*; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D003001:Cloning, Molecular / Q000379:methods*; D018076:DNA, Complementary / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology; D015723:Gene Library; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology*; D008224:Lymphoma, Follicular / Q000276:immunology; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000235:genetics / Q000276:immunology; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000235:genetics / Q000276:immunology
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018076:DNA, Complementary; C520502:GIMAP7 protein, human; D007106:Immune Sera; D007130:Immunoglobulin Idiotypes; D019151:Peptide Library; D010455:Peptides; D017412:Ribonucleoprotein, U1 Small Nuclear; C490688:SNRNP70 protein, human; D019204:GTP-Binding Proteins