Lack of toxicity of therapy-induced T cell responses against the universal tumour antigen survivin

Otto, Kerstin; Andersen, Mads Hald; Eggert, Andreas O.; Keikavoussi, Petra; Pedersen, Lars Østergaard; Rath, Jörg C.; Böck, Markus; Bröcker, Eva‐B.; Straten, Per thor; Kämpgen, Eckhart; Becker, Jürgen C.

doi:10.1016/j.vaccine.2004.08.007

Cited by 109 publications

(74 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, vaccination of a pancreatic cancer patient with a modified Survivin epitope peptide, Survivin 96-104:2M in which the second residue threonine was replaced by methionine, induced complete remission of a liver metastasis [42]. Further, vaccinations using dendritic cells loaded with Survivin 96 -104 induced positive interferon (IFN)-γ ELISPOT responses in four of five patients with advanced melanoma [21]. A recent immunohistochemical study demonstrated that 100% of adult astrocytoma specimens (n = 29; grades II-IV), but not normal brain tissues, contained Survivin-positive cells [23].…”

Section: Discussionmentioning

confidence: 99%

“…To this end, we have focused attention on the identification and characterization of human GAA-derived cytotoxic T-lymphocyte (CTL) epitopes, such as those in the interleukin-13 receptor (IL-13R)α2 [18,19] and EphA2 [20]. Recent studies by others have shown that Survivin, which contains HLA-A2-restricted CTL epitopes [21,22], are frequently expressed at high levels in grade II, III and IV astrocytomas in adults [23]. In vivo, glioma cells may undergo "immuno-editing", in which heterogeneous progressive lesions exhibit loss of specific antigens [24].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

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

show abstract

“…Peptides for immune monitoring were selected from sequences of TAA shown to be overexpressed in RCC26 cells 15 (and unpublished observations) using HLA-A*0201 motif-based epitope predictions available on the web (http://www.syfpeithi.de), or as published in the literature. Peptides specific for the following antigens were used: survivin (ELTLGEFLKL 95À104 , TLPPAWQPFL 5À14 ,) 43 ; heteroclitic survivin-related peptide (LMLGEFLKL 69À104 , 44 and EKVRRAIEQL 129À138 ); cyclin D1 (LLGATCMFV 101À109 , RLTRFLSRV 228À236 ) 45 ; adipophilin (SVASTI TGV 129À137 , TLLSNIQGV 327À335 ) 46 ; c-Met proto-oncogene (YVDPVI TSI 654À662 , VLAPGILVL 6À14 , GLIAGVVSI 31À39 ) 46 ; TYMS (VLEELLWFI, RILRKVEKI, YMIAHITGL); ILGF (AALTLLVLL, LLDGRGLCV) vimentin (DLERKVESL 218À226 , ILLAELEQL) and G250 (HLSTAFARV 217À225 ; GLLFAVTSV). Peptide synthesis was performed as described previously.…”

Section: Elispot Assaysmentioning

confidence: 99%

Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study

et al. 2010

View full text Add to dashboard Cite

Despite novel targeted agents, prognosis of metastatic renal cell cancer (RCC) remains poor, and experimental therapeutic strategies are warranted. Transfection of tumor cells with co-stimulatory molecules and/or cytokines is able to increase immunogenicity. Therefore, in our clinical study, 10 human leukocyte antigen (HLA)-A*0201 + patients with histologicallyconfirmed progressive metastatic clear cell RCC were immunized repetitively over 22 weeks with 2.5-40Â10 6 interleukin (IL)-7/CD80 cotransfected allogeneic HLA-A*0201 + tumor cells (RCC26/IL-7/CD80). Endpoints of the study were feasibility, safety, immunological and clinical responses. Vaccination was feasible and safe. In all, 50% of the patients showed stable disease throughout the study; the median time to progression was 18 weeks. However, vaccination with allogeneic RCC26/IL-7/ CD80 tumor cells was not able to induce TH1-polarized immune responses. A TH2 cytokine profile with increasing amounts of antigen-specific IL-10 secretion was observed in most of the responding patients. Interferon-g secretion by patient lymphocytes upon antigen-specific and non-specific stimulation was substantially impaired, both before and during vaccination, as compared with healthy controls. This is possibly due to profound tumor-induced immunosuppression, which may prevent induction of antitumor immune responses by the gene-modified vaccine. Vaccination in minimal residual disease with concurrent depletion of regulatory cells might be one strategy to overcome this limitation.

show abstract

“…Furthermore, overexpression of survivin in tumors is linked to decreased patient survival, increased tumor recurrence, and resistance to therapy (11), and spontaneous immune responses against survivin were recently demonstrated in various cancer patients (12). Survivin-based DNA vaccines were able to induce T cellmediated antitumor responses without severe toxicity in mouse (9) and in clinical trials (13).…”

Section: Nk Cells ͉ Nkg2d Ligands ͉ T Cells ͉ Survivin ͉ Peyer's Patchesmentioning

confidence: 99%

DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor

Zhou

Luo

Lo³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

The interaction of NKG2D, a stimulatory receptor expressed on natural killer (NK) cells and activated CD8 ؉ T cells, and its ligands mediates stimulatory and costimulatory signals to these cells. Here, we demonstrate that DNA-based vaccines, encoding syngeneic or allogeneic NKG2D ligands together with tumor antigens such as survivin or carcinoembryonic antigen, markedly activate both innate and adaptive antitumor immunity. Such vaccines result in highly effective, NK؊ and CD8 ؉ T cell-mediated protection against either breast or colon carcinoma cells in prophylactic and therapeutic settings. Notably, this protection was irrespective of the NKG2D ligand expression level of the tumor cells. Hence, this strategy has the potential to lead to widely applicable and possibly clinically useful DNA-based cancer vaccines.NK cells ͉ NKG2D ligands ͉ T cells ͉ survivin ͉ Peyer's patches

show abstract

Lack of toxicity of therapy-induced T cell responses against the universal tumour antigen survivin

Cited by 109 publications

References 18 publications

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

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

Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study

DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor

Contact Info

Product

Resources

About