A Potent Immunogenic General Cancer Vaccine That Targets Survivin, an Inhibitor of Apoptosis Proteins

Idenoue, Satomi; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Satō, Yoshihiro; Tamura, Yasuaki; Hariu, Hiroyuki; Yamamoto, Masaaki; Kurotaki, Takehiro; Tsuruma, Tetsuhiro; Asanuma, Hiroko; Kanaseki, Takayuki; Ikeda, Hideyuki; Kashiwagi, Kiyoteru; Okazaki, Masanori; Sasaki, Kohsuke; Satō, Takashi; Ohmura, Tousei; Hata, Fumitake; Yamaguchi, Koji; Hirata, Koichi; Sato, Noriyuki

doi:10.1158/1078-0432.ccr-03-0817

Cited by 114 publications

(72 citation statements)

References 39 publications

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“…Survivin-2B80-88 (refs. [74][75][76] and Survivin-2B 77 have shown the safety and therapeutic potential in cancers, such as breast cancer, colorectal cancer, and gastric cancer. SVN53-67/M57 (SurVaxM) has demonstrated its clinical potential in the treatment of gliomas and, more importantly, this vaccine contains multiple HLA epitopes that may be applicable to a large patient population.…”

Section: Discussionmentioning

confidence: 99%

Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy

et al. 2015

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Survivin, a member of the inhibitor of apoptosis protein family, is overexpressed in a variety of human neoplasms. The prognostic significance of survivin expression in diffuse large B-cell lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) is unclear. We used standard immunohistochemistry methods to quantify survivin expression in 463 patients with de novo diffuse large B-cell lymphoma who received the R-CHOP. Of the 463 patients, 269 (58%) had survivin overexpression with a cutoff of 425%, associated with an International Prognostic Index score of 42 (P = 0.015), disease in ≥ 2 extranodal sites (P = 0.011), and a high Ki-67 index (Po 0.0001). Among patients with activated B cell-like disease, the overall survival rate of survivin-positive patients was significantly lower than that of survivinnegative patients (P = 0.033); multivariate analysis confirmed that in these patients, survivin overexpression was an independent prognostic factor for survival. Among patients with wild-type p53 overexpression, the overall survival and progression-free survival rates of the survivin-positive group were significantly lower than those of the survivin-negative group (P = 0.035 and P = 0.04 respectively). In STAT3-positive patients, survivin overexpression was associated with significantly better survival. Among patients with activated B cell-like disease, survivin-positive compared with survivin-negative groups had significantly different gene expression signatures, including genes involved in mitosis or tumor cell proliferation. Our results indicate that survivin is an

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Section: Discussionmentioning

confidence: 99%

Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy

et al. 2015

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“…This has been validated in the clinic, and sera from cancer patients contain antibodies (25) and cytolytic T cells against survivin (26). This recognition has been mapped in detail (27,28), and dendritic cells pulsed with survivin peptides, or expressing survivin, elicit cytolytic T cells, which exhibit MHC-restricted anticancer activity in vitro (29,30) and in preclinical models (31). When used as an oral DNA vaccine, the survivin-directed immune response affected both tumor cells and tumor-associated angiogenesis, eradicating pulmonary metastases without toxicity in preclinical studies (32).…”

Section: Molecular Antagonistsmentioning

confidence: 97%

Targeted therapy by disablingcrossroadsignaling networks: the survivin paradigm

Altieri

2006

Molecular Cancer Therapeutics

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Embedded in the concept of targeted cancer therapy is the expectation that disabling a single oncogenic pathway will eliminate the tumor cells and leave the normal tissues unscathed. Although validated by clinical responses in certain malignancies, challenges exist to generalize this approach to most tumors, as multiple genetic lesions, chromosomal instability, insensitivity of the cancer stem cell compartment, and emergence of drug resistance complicate the identification and therapeutic exploitation of a single, driving oncogenic pathway. Instead, broader therapeutic prospects may be offered by targeting crossroad signaling networks that are selectively exploited in cancer and oversee multiple aspects of tumor cell maintenance. One such pathway is centered on survivin, a cancer gene that intersects cell proliferation, cell survival, and the cellular stress response. Several clinical trials targeting survivin with a collection of approaches from immunotherapy to small-molecule antagonists are currently under way. By simultaneously disabling multiple signaling circuitries, targeting survivin may provide a novel perspective in rational cancer therapy selective for specific cancer mechanisms but broadly applicable to disparate tumors regardless of their genetic makeup. [Mol Cancer Ther 2006;5(3):478 -82]

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“…Subsequently, we identified an HLA-A24-restricted antigenic peptide, survivin-2B 80 -88 (AYACNTSTL) recognized by CD8 ϩ CTLs (28,29). On the basis of these observations, we have started a phase I clinical study of survivin-2B 80 -88 peptide vaccination for patients with advanced colorectal cancer.…”

Section: Efficient Induction Of Tumor Peptide-specific Ctl By Immunizmentioning

confidence: 99%

Efficient Cross-Presentation by Heat Shock Protein 90-Peptide Complex-Loaded Dendritic Cells via an Endosomal Pathway

Kurotaki

Tamura

et al. 2007

The Journal of Immunology

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109

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It is well-established that heat shock proteins (HSPs)-peptides complexes elicit antitumor responses in prophylactic and therapeutic immunization protocols. HSPs such as gp96 and Hsp70 have been demonstrated to undergo receptor-mediated uptake by APCs with subsequent representation of the HSP-associated peptides to MHC class I molecules on APCs, facilitating efficient cross-presentation. On the contrary, despite its abundant expression among HSPs in the cytosol, the role of Hsp90 for the cross-presentation remains unknown. We show here that exogenous Hsp90-peptide complexes can gain access to the MHC class I presentation pathway and cause cross-presentation by bone marrow-derived dendritic cells. Interestingly, this presentation is TAP independent, and followed chloroquine, leupeptin-sensitive, as well as cathepsin S-dependent endosomal pathways. In addition, we show that Hsp90-chaperoned precursor peptides are processed and transferred onto MHC class I molecules in the endosomal compartment. Furthermore, we demonstrate that immunization with Hsp90-peptide complexes induce Ag-specific CD8+ T cell responses and strong antitumor immunity in vivo. These findings have significant implications for the design of T cell-based cancer immunotherapy.

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A Potent Immunogenic General Cancer Vaccine That Targets Survivin, an Inhibitor of Apoptosis Proteins

Cited by 114 publications

References 39 publications

Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy

Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy

Targeted therapy by disablingcrossroadsignaling networks: the survivin paradigm

Efficient Cross-Presentation by Heat Shock Protein 90-Peptide Complex-Loaded Dendritic Cells via an Endosomal Pathway

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