Publication Date:
2005-11-16
Description:
Active immunization of follicular lymphoma patients with idiotypic vaccines elicits antigen-specific antibody responses, T-cell responses, and antitumor effects (Bendandi, M. et al., Nat Med5, 1171). 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. We further hypothesize that these antigens may represent tumor rejection targets for immunotherapy. 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. To further determine the specificity of these patients’ post vaccine sera, the corresponding FL-aa-7 and FL-aa-18 peptides were synthesized and tested for serum binding. As expected, post-vaccine but not pre-vaccine or normal, specifically bound the FL-aa-7 and FL-aa-18 peptides, respectively. Furthermore, both peptides specifically inhibited the binding of post-vaccine sera to the respective FL-aa-7 and FL-aa-18 phage clones in a dose-dependent manner. These data suggest that Id vaccinated patients generated specific antibodies to novel peptides FL-aa-7 and FL-aa-18, unrelated to Id. Overall, these data indicate that Id-vaccinated B cell lymphoma patients mounted antibody responses specifically for FL-aa-7-1 and FL-aa-18 peptides, which may represent a potential immunotherapeutic tumor antigen. The clinical and biological relevance of the response is to be elucidated.
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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