Abstract
Immunization with tumor antigens induces cellular and humoral immune responses. These responses by T cells are specific for defined epitopes (determinants) in the molecule of the immunizing tumor antigen. Extension of such responses to self-antigens requires induction of autoimmunity to the tumor. As with systems of autoimmune disease, expression of T cell autoimmunity is charaterized by diversification of responses from the inducer determinant to other responder (cryptic) determinants. Since similar strategies may be useful for therapy of human cancers, we investigated whether the induction of response to a HER-2 peptide F7 (776–789) induces enhanced reactivity of other HER-2 peptides. We found that stimulation with F7 can expand a response to another epitope F13 (884–899) in both an ovarian cancer patient with progressive disease and a healthy donor who shared HLA-DR11. This response was characterized mainly by increased interferon γ secretion, and proliferation, but was not observed with another donor who shared HLA-DR14 and HLA-DQ5 with the patient. Since repeated vaccination with the same epitope may lead to a decline of primary cell reactivity caused by apoptosis spreading the response to other epitopes, the tumor antigen may provide an approach for maintaining an inflammatory Th1 response during cancer vaccination.
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Received: 10 April 2000 / Accepted: 12 July 2000
Rights and permissions
About this article
Cite this article
Anderson, B., Kudelka, A., Honda, T. et al. Induction of determinant spreading and of Th1 responses by in vitro stimulation with HER-2 peptides. Cancer Immunol Immunother 49, 459–468 (2000). https://doi.org/10.1007/s002620000143
Issue Date:
DOI: https://doi.org/10.1007/s002620000143