Survivin is a shared tumor-associated antigen expressed in a broad variety of malignancies and recognized by specific cytotoxic T cells

Schmidt, Susanne; Schag, Kerstin; Müller, Martin; Weck, Markus M.; Appel, Silke; Kanz, Lothar; Grünebach, Frank; Brossart, Peter

doi:10.1182/blood-2002-08-2554

Cited by 245 publications

(175 citation statements)

References 28 publications

Supporting

Mentioning

166

Contrasting

Order By: Relevance

“…This is reflected by the emergence of antigen-specific CD8 þ T cells in the peripheral blood of AML patients following transplantation. Such CTL responses have been reported against a broad range of AML-related tumor antigens, including HOXA9 (HOXA9 146-154 ), 62 hTERT (hTERT 540-548 ), 62 27,62 and RAGE-1 (RAGE-1 [11][12][13][14][15][16][17][18][19][20] (Table 1). 79 NuSAP1 has been identified as a target of humoral immunity following allogeneic HSCT.…”

Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respmentioning

confidence: 83%

“…This is the case for LAAs possessing highly restricted levels of expression in normal cell types, such as human telomerase reverse transcriptase (hTERT) 17 and survivin. 18 In view of their role in promoting unrestrained cell growth and survival, it is not surprising to find the overexpression of these proteins in a wide variety of human cancers and the absence of expression in normal, non-dividing or terminally differentiated cells. 18 Their relatively restricted expression in normal tissues, along with their abundant expression in cancer cells, make hTERT and survivin attractive targets for antigen-specific immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…18 In view of their role in promoting unrestrained cell growth and survival, it is not surprising to find the overexpression of these proteins in a wide variety of human cancers and the absence of expression in normal, non-dividing or terminally differentiated cells. 18 Their relatively restricted expression in normal tissues, along with their abundant expression in cancer cells, make hTERT and survivin attractive targets for antigen-specific immunotherapy. Recently, however, some concern has been raised regarding survivin expression in normal, activated T cells, which could cause these cells to become targets of survivinspecific cytotoxic T lymphocytes (CTLs).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

2012

View full text Add to dashboard Cite

The graft-versus-leukemia effect of allogeneic hematopoietic stem cell transplantation (HSCT) has shown that the immune system is capable of eradicating acute myeloid leukemia (AML). This knowledge, along with the identification of the target antigens against which antileukemia immune responses are directed, has provided a strong impetus for the development of antigen-targeted immunotherapy of AML. The success of any antigen-specific immunotherapeutic strategy depends critically on the choice of target antigen. Ideal molecules for immune targeting in AML are those that are: (1) leukemia-specific; (2) expressed in most leukemic blasts including leukemic stem cells; (3) important for the leukemic phenotype; (4) immunogenic; and (5) clinically effective. In this review, we provide a comprehensive overview on AML-related tumor antigens and assess their applicability for immunotherapy against the five criteria outlined above. In this way, we aim to facilitate the selection of appropriate target antigens, a task that has become increasingly challenging given the large number of antigens identified and the rapid pace at which new targets are being discovered. The information provided in this review is intended to guide the rational design of future antigen-specific immunotherapy trials, which will hopefully lead to new antileukemia therapies with more selectivity and higher efficacy.

show abstract

Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

2012

View full text Add to dashboard Cite

show abstract

“…Survivin is overexpressed in most human cancers, and inhibition of its function results in increased apoptosis [39]. Induction of cytotoxic immunity against Survivin may, therefore, be an attractive strategy [40]. Survivin has multiple T cell epitopes, including Survivin 96-104 as an HLA-A2-restricted CTL epitope [22,41].…”

Section: Discussionmentioning

confidence: 99%

Expression of glioma-associated antigens in pediatric brain stem and non-brain stem gliomas

et al. 2008

View full text Add to dashboard Cite

We investigated the protein expression of three glioma-associated antigens (GAAs) in pediatric brain stem glioma (BSG) and non-brain stem glioma (NBSG) cases with a view to their possible use in immunotherapy. Expression of EphA2, IL-13Rα2 and Survivin were studied by immunohistochemistry on paraffin-embedded tissues using a series of 15 BSG cases and 12 NBSG cases. Thirteen of 15 BSGs and all 12 NBSGs expressed at least one of GAAs; and 7 BSGs and 9 NBSGs expressed at least two of these GAAs at higher levels than non-neoplastic brain. There was no association between the tumor grade and levels of GAA expression. Although many cases demonstrated diffuse expression of GAAs throughout specimens, partial or patchy expression was noted in a small number of cases, suggesting a need for targeting multiple GAAs in immunotherapy. These results suggest that EphA2, IL-13Ralpha2 and Survivin are suitable targets for developing vaccine strategies for pediatric glioma.

show abstract

“…32,49 Accordingly, survivin is expected to be a suitable and universal target for tumor screening and may be useful in immunotherapy and gene therapy designed to defeat cancer. 54,55 Furthermore, evidence is now accumulating that the expression level of survivin contributes to the clinical outcome of tumors, including prognosis, susceptibility to anti-cancer drugs, and malignant behavior. 56,57 Recent studies indicate the potential clinical relevance of survivin quantified by real-time PCR in ATL.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional activation of survivin through the NF‐κB pathway by human T‐cell leukemia virus type I tax

Kawakami

Tomita

Matsuda

et al. 2005

Intl Journal of Cancer

142

112

View full text Add to dashboard Cite

Survivin, a unique member of the inhibitor of apoptosis protein family, is overexpressed in many cancers and considered to play an important role in oncogenesis. We previously reported the survivin expression profile in ATL, a CD4-positive T-cell malignancy caused by HTLV-I. HTLV-I Tax is thought to play an important role in immortalization of T cells. We have shown also that the expression of Tax protected the mouse T-cell line CTLL-2 against apoptosis induced by deprivation of IL-2 and converted its growth from being IL-2 dependent to being IL-2 independent through the NF-kB pathway. In our study, we demonstrate that constitutive expression of survivin was associated with resistance to apoptosis after IL-2 deprivation in Tax-expressing CTLL-2 cells. Transient transfection assays showed that survivin promoter was transactivated by Tax, via the activation of NF-kB. Pharmacological NFkB inhibition resulted in suppression of survivin expression and caused apoptosis of Tax-expressing CTLL-2 cells. Our findings suggest that activated NF-kB signaling contributes directly to malignant progression of ATL by preventing apoptosis, acting through the prosurvival protein survivin. ' 2005 Wiley-Liss, Inc.

show abstract

Survivin is a shared tumor-associated antigen expressed in a broad variety of malignancies and recognized by specific cytotoxic T cells

Cited by 245 publications

References 28 publications

Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

Expression of glioma-associated antigens in pediatric brain stem and non-brain stem gliomas

Transcriptional activation of survivin through the NF‐κB pathway by human T‐cell leukemia virus type I tax

Contact Info

Product

Resources

About