Vaccination against the HER-2/neu oncogenic protein.

Bernhard, Helga; Salazar, Lupe G.; Schiffman, Kathy; Smorlesi, Arianna; Schmidt, Burkhard; Knutson, Keith L.; Disis, Mary L.

doi:10.1677/erc.0.0090033

Cited by 52 publications

(33 citation statements)

References 68 publications

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“…A novel approach toward the treatment of HER-2-positive breast cancer has been the use of vaccines and adoptive immunotherapy targeting HER-2 ECD [367][368][369][370][371]. HER-2-specific vaccines have been tested in human clinical trials that have shown that significant levels of durable T-cell HER-2 immunity can be generated with active immunization.…”

Section: Her-2 Vaccinesmentioning

confidence: 99%

“…HER-2-specific vaccines have been tested in human clinical trials that have shown that significant levels of durable T-cell HER-2 immunity can be generated with active immunization. No significant autoimmunity directed against normal tissues has been encountered [368]. Moreover, active anti-HER-2 immunization could facilitate the ex vivo expansion of HER-2-specific T cells for use in adoptive immunotherapy for the treatment of established metastatic disease [367].…”

Section: Her-2 Vaccinesmentioning

confidence: 99%

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The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine

et al. 2009

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1. Contrast the current strengths and limitations of the three main slide-based techniques (IHC, FISH, and CISH) currently in clinical use for testing breast cancer tissues for HER-2 status.2. Compare the efficacy of trastuzumab-and lapatinib-based regimens in the adjuvant and metastatic settings as reported in published clinical trials and regulatory approval databases.3. Contrast the list of biomarkers that have been associated with clinical resistance to trastuzumab and lapatinib and describe their current level of validation.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTThe human epidermal growth factor receptor (HER-2) oncogene encodes a transmembrane tyrosine kinase receptor that has evolved as a major classifier of invasive breast cancer and target of therapy for the disease. The validation of the general prognostic significance of HER-2 gene amplification and protein overexpression in the absence of anti-HER-2 targeted therapy is discussed in a study of 107 published studies involving 39,730 patients, which produced an overall HER-2-positive rate of 22.2% and a mean relative risk for overall survival (OS) of 2.74. The issue of HER-2 status in primary versus metastatic breast cancer is considered along with a section on the features of metastatic HER-2-positive disease. The major marketed slide-based HER-2 testing approaches, immunohistochemistry, fluorescence in situ hybridization, and chromogenic in situ

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Section: Her-2 Vaccinesmentioning

confidence: 99%

Section: Her-2 Vaccinesmentioning

confidence: 99%

The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine

et al. 2009

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“…3 Several strategies against HER2/neu have been proposed and DNA vaccination represents an optimal methodology for activating the immune system against HER2/neu. 4 Various studies, some of which were carried out by our group, confirmed the possibility of inducing HER2/neu-specific immunity in HER2/neu transgenic mice by DNA vaccination with plasmids encoding fulllength or truncated HER2/neu. [5][6][7][8][9] In the investigated models, DNA vaccination inhibited tumour development according to vaccine properties; the use of molecules playing critical regulatory and signalling roles in immunity, such as immunomodulatory cytokines and costimulatory molecules, increased the effectiveness of DNA vaccines in terms of tumour prevention.…”

Section: Introductionmentioning

confidence: 97%

Imiquimod and S-27609 as adjuvants of DNA vaccination in a transgenic murine model of HER2/neu-positive mammary carcinoma

et al. 2005

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DNA vaccination against HER-2/neu is an effective way to induce an immune response able to oppose the spontaneous development of mammary tumours occurring in HER-2/neu transgenic mice. In this study, we have evaluated the potential of Imiquimod and the analogue S-27609 as adjuvants of DNA vaccination against HER-2/neu in transgenic mice. The association of a DNA vaccine encoding a portion of rat HER2/neu with either Imiquimod or S-27609 was found to delay the development of spontaneous mammary tumours and to reduce their incidence, in comparison with DNA vaccination alone. Almost 80 or 40% of tumour-free mice were found at the end of measurement time in mice vaccinated and supplemented with Imiquimod or S-27609, respectively. The antitumour preventive effect was associated with increased antibody and cell-mediated immune responsiveness against HER-2/neu. In mice vaccinated and supplemented with Imiquimod, a small but significant increase of rat p185 neu -specific cytotoxicity and of IFN-g and IL-2-producing CD8T cells, together with a reduction of IL-4-producing CD4T cells, and a switch from an IgG1 towards a IgG2a phenotype of anti-p185 neu antibodies, suggested a TH1 polarization of the immune response. The immunoregulatory efficacy of S-27609 was lower than that observed for Imiquimod. These data highlight the potential of Imiquimod, and, to a lower extent, of S-27609, as immunological adjuvants of therapeutic DNA vaccines.

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“…Examples of CTAs currently being used for immunotherapy include NY-ESO-1 and MAGE-A3 peptides in melanoma (Coulie et al, 2001;Jäger et al, 2001). However, it should be noted that other categories of SEREX antigens, such as the overexpressed HER-2/neu protein, are being targeted with some success in the treatment of breast carcinomas (Bernhard et al, 2002). SEREX antigens can also be used as adjuvants to boost the immune response to other tumour antigens (Nishikawa et al, 2001).…”

mentioning

confidence: 99%

A novel diffuse large B-cell lymphoma-associated cancer testis antigen encoding a PAS domain protein

et al. 2004

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Here we report that the OX-TES-1 SEREX antigen, which showed immunological reactivity with serum from four out of 10 diffuse large B-cell lymphoma (DLBCL) patients, is encoded by a novel gene, PAS domain containing 1 (PASD1). PASD1_v1 cDNA encodes a 639 amino-acid (aa) protein product, while an alternatively spliced variant (PASD1_v2), lacking intron 14, encodes a 773 aa protein, the first 638 aa of which are common to both proteins. The PASD1-predicted protein contains a PAS domain that, together with a putative leucine zipper and nuclear localisation signal, suggests it encodes a transcription factor. The expression of PASD1_v1 mRNA was confirmed by RT -PCR in seven DLBCL-derived cell lines, while PASD1_v2 mRNA appears to be preferentially expressed in cell lines derived from non-germinal centre DLBCL. Immunophenotyping studies of de novo DLBCL patients' tumours with antibodies to CD10, BCL-6 and MUM1 indicated that two patients mounting an immune response to PASD1 were of a poor prognosis nongerminal centre subtype. Expression of PASD1 mRNA was restricted to normal testis, while frequent expression was observed in solid tumours (25 out of 68), thus fulfilling the criteria for a novel cancer testis antigen. PASD1 has potential for lymphoma vaccine development that may also be widely applicable to other tumour types.

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Vaccination against the HER-2/neu oncogenic protein.

Abstract: The HER-

Cited by 52 publications

References 68 publications

The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine

The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine

Imiquimod and S-27609 as adjuvants of DNA vaccination in a transgenic murine model of HER2/neu-positive mammary carcinoma

A novel diffuse large B-cell lymphoma-associated cancer testis antigen encoding a PAS domain protein

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