Activation of Tumor Antigen-Specific Cytotoxic T Lymphocytes (CTLs) by Human Dendritic Cells Infected with an Attenuated Influenza A Virus Expressing a CTL Epitope Derived from the HER-2/neu Proto-Oncogene

Efferson, Clay L.; Schickli, Jeanne H.; Ko, Byung Kyum; Kawano, Keiichi; Mouzi, Sara; Palese, Peter; Garcı́a-Sastre, Adolfo; Ioannides, Constantin G.

doi:10.1128/jvi.77.13.7411-7424.2003

Cited by 23 publications

(20 citation statements)

References 52 publications

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“…However, heat shock proteins bound to RNAs can act as coactivators of RNA receptors by presenting some and masking other RNA sequences similar with tumor and viral peptides bound on peptidoglycans, which increase IL-6 production from iDC. 10 Our findings suggest that TA from ISMMC is delivered to endosomes and reach the cytoplasm for proteasomal processing. This retrotranslocation pathway consists of transport of pCE through the route lysosomes !…”

Section: Discussionmentioning

confidence: 89%

“…P and R 2 values were calculated with the program Statview (Microsoft Excel). 10 Western blotting. Western blotting was performed as described previously (10).…”

Section: Methodsmentioning

confidence: 99%

“…10 Western blotting. Western blotting was performed as described previously (10). Proteins were quantified by scanning densitometry using the Image J1.34 software, version 1.61.…”

Section: Methodsmentioning

confidence: 99%

“…Ag-specific CD8 + T cells were considered to express high (hi), medium (med), and low (lo) numbers of E75-TCR based on the levels of MFI (E75-TCR; 10 , respectively) after interaction with E75-HLA-A2-IgG dimers (10).…”

Section: Methodsmentioning

confidence: 99%

“…All assays were performed as we described previously (10,12). IL-12 and IFN-g were quantified 48 h after stimulation from the same culture.…”

Section: Methodsmentioning

confidence: 99%

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Taxol Increases the Amount and T Cell–Activating Ability of Self-Immune Stimulatory Multimolecular Complexes Found in Ovarian Cancer Cells

et al. 2007

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It has been proposed that chemotherapy enhances tumor antigen (TA)-specific immunity. The molecular form of TA from ovarian tumor that activates cellular immunity is unknown. We report here identification of a novel molecular form of immunogenic TA for CD8 + cells named self-immune stimulatory multimolecular complexes (ISMMC). ISMMC consist of a molecular complex of polyosome/ribosome-bound ubiquitinated nascent HER-2 polypeptides. This complex is chaperoned by heat shock protein Gp96, which mediates ISMMC uptake by antigen-presenting cells through the scavenger receptor CD91. RNAs in ISMMC stimulate immature dendritic cells to secrete interleukin 12 and induce IFN-; in peripheral blood mononuclear cells. ISMMC dissociate, retrotranslocate from the lysosome to cytoplasm, and are processed to peptides by the proteasome. At subpharmacologic doses, Taxol increased the amount of ISMMC by three to four times and modified their composition by inducing the attachment of cochaperones of HSP70, such as the mitoticphase phosphoprotein 11J. On a total protein basis, Taxol induced ISMMC, expanded more CD8 + cells, activated more CD56 + NKG2D + cells to produce IFN-;, and were more potent inducers of high T-cell receptor density Perforin + cells than native ISMMC and peptide E75. Elucidation of the composition of ISMMC and identification of adducts formed by Taxol should be important for developing molecular cancer vaccines. [Cancer Res 2007;67(17):8378-87]

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Section: Discussionmentioning

confidence: 89%

“…P and R 2 values were calculated with the program Statview (Microsoft Excel). 10 Western blotting. Western blotting was performed as described previously (10).…”

Section: Methodsmentioning

confidence: 99%

“…10 Western blotting. Western blotting was performed as described previously (10). Proteins were quantified by scanning densitometry using the Image J1.34 software, version 1.61.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…All assays were performed as we described previously (10,12). IL-12 and IFN-g were quantified 48 h after stimulation from the same culture.…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Taxol Increases the Amount and T Cell–Activating Ability of Self-Immune Stimulatory Multimolecular Complexes Found in Ovarian Cancer Cells

et al. 2007

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HER‐2: A biomarker at the crossroads of breast cancer immunotherapy and molecular medicine

Pupa

Tagliabue

Ménard

et al. 2005

Journal Cellular Physiology

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The oncoprotein encoded by the HER-2 oncogene is a member of the HER family of receptor tyrosine kinases and is actually the first successfully exploited target molecule in new biomolecular therapies of solid tumors. The association of HER-2 overexpression with human tumors, its extracellular accessibility, as well as its involvement in tumor aggressiveness are all factors that make this receptor an appropriate target for tumor-specific therapy. In addition, HER-2 overexpression fosters its immunogenicity, as shown by the frequency of B and T cell-mediated responses against this oncoprotein in cancer patients, and it is being investigated as a promising molecule for either passive and active immunotherapy strategies. This review summarizes a number of immune intervention approaches that target HER-2 in breast cancer.

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Interferon Antagonists of Influenza Viruses

Garcı́a-Sastre

Modulation of Host Gene Expression and Innate Immunity by Viruses

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Activation of Tumor Antigen-Specific Cytotoxic T Lymphocytes (CTLs) by Human Dendritic Cells Infected with an Attenuated Influenza A Virus Expressing a CTL Epitope Derived from the HER-2/neu Proto-Oncogene

Cited by 23 publications

References 52 publications

Taxol Increases the Amount and T Cell–Activating Ability of Self-Immune Stimulatory Multimolecular Complexes Found in Ovarian Cancer Cells

Taxol Increases the Amount and T Cell–Activating Ability of Self-Immune Stimulatory Multimolecular Complexes Found in Ovarian Cancer Cells

HER‐2: A biomarker at the crossroads of breast cancer immunotherapy and molecular medicine

Interferon Antagonists of Influenza Viruses

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