Six-Transmembrane Epithelial Antigen of the Prostate as an Immunotherapeutic Target for Renal Cell and Bladder Cancer

Azumi, Makoto; Kobayashi, Hiroya; Aoki, Naoko; Sato, Keisuke; Kimura, Shoji; Κakizaki, Hidehiro; Tateno, Masatoshi

doi:10.1016/j.juro.2009.12.094

Cited by 30 publications

(27 citation statements)

References 14 publications

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“…In this study, the prediction system could select nine peptide sequences from EZH2 (data not shown) and we selected the three highest potentially promiscuous peptides, EZH2 95-109 , EZH2 220-234 and EZH2 693-704 . In the case of STEAP, the algorithm system suggested 28 peptide sequences (data not shown) as potentially promiscuous HLA-class II binders and we have reported that two STEAP peptides, STEAP 102-116 and STEAP 192-206 were effective in stimulating in vitro anti-tumor T helper responses [18,19]. In the present study, considering that an ideal TAA should contain peptide epitopes to stimulate both CD8 and CD4 T-cells, we selected 2 STEAP peptides from these promiscuous binders, STEAP 261-275 , which overlaps with HLA-A2-restricted CD8 T-cell epitope STEAP 262-270 [20] and STEAP 281-296 , which lies proximal to HLA-A2-restricted CD8 epitope, STEAP 292-300 [21].…”

Section: Resultsmentioning

confidence: 99%

“…In view of this, we believe that identifying TAAs and the corresponding peptide epitopes capable of eliciting anti-tumor T-cell responses will be critical to develop peptide-based cancer immunotherapy. EZH2 plays a role in cell cycle regulation and proliferation and increased EZH2 expression has been correlated with aggressive tumor behavior and poor survival in LC [18]. STEAP is overexpressed in various types of tumors including LC.…”

Section: Discussionmentioning

confidence: 99%

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Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 as immunotherapeutic targets for lung cancer

et al. 2011

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BackgroundT-cell based immunotherapy for lung cancer (LC) could be a promising and novel therapeutic approach. Six-transmembrane epithelial antigen of the prostate (STEAP) and the polycomb group protein enhancer of zeste homolog 2 (EZH2) are highly expressed in LC and since the expression of molecules in normal tissue is significantly lower as compared to tumor cells, these proteins are considered as potential tumor-associated antigens (TAAs) for developing T-cell based immunotherapy.MethodsWe assessed the capacity of predicted CD4 T-cell epitopes from STEAP and EZH2 to induce anti-tumor immune responses to LC cell lines.ResultsOut of several predicted epitopes, two synthetic peptides, STEAP281-296 and EZH295-109, were effective in inducing CD4 T-cell responses that were restricted by HLA-DR1, DR15, or DR53 molecules, indicating that the peptides function as promiscuous T-cell epitopes. Moreover, STEAP281-296 and EZH295-109-reactive T-cells could directly recognize STEAP or EZH2 expressing LC cells in an HLA-DR restricted manner. In addition, some STEAP-reactive T-cells responded to STEAP+ tumor cell lysates presented by autologous dendric cells. Most significantly, both of these peptides were capable of stimulating in vitro T-cell responses in patients with LC.ConclusionsPeptides STEAP281-296 and EZH295-109 function as strong CD4 T-cell epitopes that can elicit effective anti-tumor T-cell responses against STEAP or EZH2 expressing LC. These observations may facilitate the translation of T-cell based immunotherapy into the clinic for the treatment of LC.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 as immunotherapeutic targets for lung cancer

et al. 2011

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“…As a TAA, STEAP1 was also thought to be able to trigger an immune response to eliminate a tumor by specifically eliciting CD4 þ helper T cells. Consequently, 2 specific synthetic STEAP1 peptides, STEAP 102-116 (HQQYFYKIPILVINK) and STEAP [192][193][194][195][196][197][198][199][200][201][202][203][204][205][206] (LLNWAYQQVQQNKED), which strongly bind to different classes of HLA-DR, can also be presented by those different classes to CD4 þ helper T cells (74,78 (79). In fact, both of these peptides were identified as being processed endogenously, through direct presentation of STEAP1 peptides by HLA-DR molecules, and exogenously, by APCs that process STEAP1 peptides derived from cell lysates, as seen in vitro with renal and bladder cancer (78).…”

Section: Steap Proteins As Immunotherapeutic Targetsmentioning

confidence: 99%

STEAP Proteins: From Structure to Applications in Cancer Therapy

Gomes

Maia²,

Santos³

2012

Molecular Cancer Research

169

214

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The human 6-transmembrane epithelial antigen of prostate (STEAP) family comprises STEAP1, STEAP2, STEAP3, and STEAP4. All of these proteins are unique to mammals and share an innate activity as metalloreductases, indicating their importance in metal metabolism. Overall, they participate in a wide range of biologic processes, such as molecular trafficking in the endocytic and exocytic pathways and control of cell proliferation and apoptosis. STEAP1 and STEAP2 are overexpressed in several types of human cancers, namely prostate, bladder, colon, pancreas, ovary, testis, breast, cervix, and Ewing sarcoma, but their clinical significance and role in cancer cells are not clear. Still, their localization in the cell membrane and differential expression in normal and cancer tissues make STEAP proteins potential candidates as biomarkers of several cancers, as well as potential targets for new immunotherapeutic strategies for disease attenuation or treatment. This review brings together the current knowledge about each STEAP protein, giving an overview of the roles of this family of proteins in human physiology and disease, and analyzes their potential as immunotherapeutic agents in cancer research. Mol Cancer Res; 10(5); 573-87. Ó2012 AACR. IntroductionThe 6-transmembrane epithelial antigen of prostate (STEAP) family of proteins includes 4 members, named 6-transmembrane epithelial antigen of prostate 1 to 4 (STEAP1-STEAP4). They all have in common a 6-transmembrane domain, a COOH-terminal domain with significant homology to the yeast FRE family of b-type cytochrome metalloreductases, and an N-terminal with homology to the archaeal and bacterial F 420 H 2 :NADP

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“…An immunization with recombinant DNA or modified vaccinia virus Ankara vector delivering STEAP1 antigen inhibited prostate cancer progression in a murine subcutaneous syngeneic tumor model [6]. Targeting STEAP1 appeared also useful for Tcell based immunotherapy in renal and bladder cancers [7]. Finally, STEAP1 was also described as an attractive target for antibody therapy in multiple solid tumors including prostate, renal and bladder cancers [3].…”

Section: Introductionmentioning

confidence: 99%

STEAP1 is overexpressed in cancers: A promising therapeutic target

Moreaux

Kassambara

Hose

et al. 2012

Biochemical and Biophysical Research Communications

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The six-transmembrane epithelial antigen of prostate (STEAP) protein was identified in advanced prostate cancer and is up-regulated in multiple cancer cell lines, including prostate, bladder, colon, ovarian, and Ewing sarcoma. STEAP1 was described as a suitable antigen for T-cell-based or antibody-based immunotherapy.We have investigated the expression of STEAP1 in 40 human tumor types -brain, epithelial, lymphoid -and in their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database. STEAP1 was found significantly overexpressed in 11 cancers. In addition, high STEAP1 expression was associated with poor overall survival in colorectal cancer, diffuse large B cell lymphoma, acute myeloid leukemia and multiple myeloma.Taken together, these data suggest that STEAP1 is a potential therapeutic target for Tcell based immunotherapy or antibody therapy in a large panel of cancers.3

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Six-Transmembrane Epithelial Antigen of the Prostate as an Immunotherapeutic Target for Renal Cell and Bladder Cancer

Abstract: Results show that STEAP helper T-lymphocyte epitopes could be used to optimize T-cell based immunotherapy against STEAP expressing renal cell and bladder cancer.

Cited by 30 publications

References 14 publications

Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 as immunotherapeutic targets for lung cancer

Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 as immunotherapeutic targets for lung cancer

STEAP Proteins: From Structure to Applications in Cancer Therapy

STEAP1 is overexpressed in cancers: A promising therapeutic target

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