Cellular immunity to the Her-2/neu protooncogene

Biologic and therapeutic role of HER2 in cancer

“…HER2-derived vaccines have been used in efforts to redirect immunity to induce rejection of HER2-positive tumors (Foy et al, 2002;Kiessling et al, 2002). Immunization regimens of active immunotherapy have been devised that generate specific T-cell responses with or without accompanying antibody responses and are currently being tested in animal models or in clinical trials (Rovero et al, 2000;Di Carlo et al, 2001;Nanni et al, 2001;Foy et al, 2002;Kiessling et al, 2002).…”

“…Immunotherapeutic strategies such as immunization with MHC class I-and class II-restricted HER2-specific peptides with or without adjuvants, HER2 DNA, HER2 recombinant protein, and dendritic cells loaded with HER2 peptides are now being tested in animal models and phase I clinical trials (Knutson et al, 2001;Disis et al, 2002;Foy et al, 2002;Kiessling et al, 2002). The vaccine preparation consisted of HER2 peptides containing putative T-helper epitopes and HLA-A2-binding Role of HER2 in cancer S Menard et al motifs, with recombinant human GM-CSF administered as adjuvant.…”

Improved Immunogenicity of an Immunodominant Epitope of the Her-2/neu Protooncogene by Alterations of MHC Contact Residues

“…Therefore, it is expected that this tumor Ag may be weakly immunogenic, and that most T cells specific for this Ag are clonally eliminated or subjected to tolerance in the periphery. Yet accounts from experimental models and clinical trials confirm that HER-2 can be immunogenic and generate Ab, CTL, and Th cell responses in subjects bearing HER-2-overexpressing tumors (5). Results from murine neu transgenic experimental models further illustrate that HER-2-based vaccines can induce tumor protection (7).…”

“…HER-2 is a nonmutated, overexpressed oncogene that encodes a 185-kDa transmembrane, receptor-like glycoprotein with tyrosine kinase activity and is expressed in a broad spectrum of human carcinomas. Several properties render HER-2 a promising candidate for T cell-based tumor vaccination strategies (5). Of particular importance, HER-2 overexpression appears to contribute not only to disease initiation and progression, but also to the transformation of human mammary epithelium.…”

CCL19 as an adjuvant for intradermal gene gun immunization in a Her2/neu mouse tumor model: improved vaccine efficacy and a role for B cells as APC

“…The preclinical Her2/neu mouse tumor model used in the current study is well established and has previously been applied in other investigations. [27][28][29] It is particularly appropriate for the initial evaluation of adjuvants for genetic immunization and successful candidate molecules may subsequently be evaluated in transgenic mouse models, which are more suitable with regard to the preexisting tolerance towards tumor antigens observed in patients. 30 Intramuscular application of pDNA(Her2/neu) alone was not able to induce protection from a subsequent tumor challenge, whereas intradermal delivery of the same vaccine by gene gun led to longterm protection in 40% of the animals.…”