title: Induction of determinant spreading and of Th1 responses by in vitro stimulation with HER-2 peptides.
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 gamma 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.
authors.affiliation: Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: B W
authors.initials: BW
authors.lastname: Anderson
authors.forename: A P
authors.initials: AP
authors.lastname: Kudelka
authors.forename: T
authors.initials: T
authors.lastname: Honda
authors.forename: M S
authors.initials: MS
authors.lastname: Pollack
authors.forename: D M
authors.initials: DM
authors.lastname: Gershenson
authors.forename: M A
authors.initials: MA
authors.lastname: Gillogly
authors.forename: J L
authors.initials: JL
authors.lastname: Murray
authors.forename: C G
authors.initials: CG
authors.lastname: Ioannides
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism / Q000627:therapeutic use; D017209:Apoptosis; D016022:Case-Control Studies; D002455:Cell Division; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005260:Female; D006683:HLA-DQ Antigens / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D059810:HLA-DR Serological Subtypes; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D010455:Peptides / Q000276:immunology / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000951:Antigens, Neoplasm; D000939:Epitopes; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; D007371:Interferon-gamma; D007376:Interleukin-2; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases; C410042:HLA-DQ5 antigen; C080766:HLA-DR11 antigen; C052238:HLA-DR14