Induction of Adipophilin-Specific Cytotoxic T Lymphocytes Using a Novel HLA-A2-Binding Peptide That Mediates Tumor Cell Lysis

Schmidt, Susanne; Schag, Kerstin; Müller, Martin; Weinschenk, Toni; Appel, Silke; Schoor, Oliver; Weck, Markus M.; Grünebach, Frank; Kanz, Lothar; Stevanović, Stefan; Rammensee, Hans‐Georg; Brossart, Peter

doi:10.1158/0008-5472.can-03-2538

Cited by 59 publications

(35 citation statements)

References 19 publications

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“…ADFP, C-MET, and RSG-5 are not immunogenic in patients with ccRCC, as we did not detect T-cell responses specific for these antigens, despite their frequent overexpression. This finding is in agreement with previously published data on rare T-cell responses in patients with ccRCC (15), even though ADFP-and C-MET-specific T cells could be expanded from the blood of healthy donors (33,34). RGS-5 overexpression did not result in detectable RGS-5-specific T-cell responses in our cohort, although such responses were reported in the blood of healthy donors and patients with acute myeloid leukemia (42).…”

Section: Discussionsupporting

confidence: 93%

“…In addition to CA-IX, ADFP, Cyclin D1, C-MET, and RGS-5 are also overexpressed in ccRCC (14). In contrast to published reports (33,34), we found that ADFP expressed more frequently (65%) than C-MET (30%). Cyclin D1 is a cell-cycle regulator crucial for the G 1 -S transition (35) and is overexpressed in many cancers including colorectal and breast carcinoma (36,37).…”

Section: Discussioncontrasting

confidence: 93%

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Spontaneous Peripheral T-cell Responses toward the Tumor-Associated Antigen Cyclin D1 in Patients with Clear Cell Renal Cell Carcinoma

Dannenmann

Hermanns

Bransi

et al. 2013

Cancer Immunology Research

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Renal cell carcinoma (RCC) is a heterogeneous group of kidney cancers with clear cell RCC (ccRCC) as the major subgroup. To expand the number of clinically relevant tumor-associated antigens (TAA) that can be targeted by immunotherapy, we analyzed samples from 23 patients with primary ccRCC for the expression and immunogenicity of various TAAs. We found high-frequency expression of MAGE-A9 and NY-ESO-1 in 36% and 55% of samples, respectively, and overexpression of PRAME, RAGE-1, CA-IX, Cyclin D1, ADFP, C-MET, and RGS-5 in many of the tumor samples. We analyzed the blood of patients with HLA-A2 þ ccRCC for the presence of CD8 þ T cells specific for TAA-derived HLA-A2-restricted peptides and found spontaneous responses to cyclin D1 in 5 of 6 patients with Cyclin D1-positive tumors. Cyclin D1-specific CD8 þ T cells secreted TNF-a, IFN-g, and interleukin-2 (IL-2), and degranulated, indicating the presence of polyfunctional tumor-specific CD8 þ T cells in the blood of these patients with ccRCC. The high frequency (43%) of Cyclin D1 overexpression and the presence of functional cyclin D1-specific T cells in 83% of these patients with ccRCC suggest that cyclin D1 may be a target for immunotherapeutic strategies. Cancer Immunol Res; 1(5); 288-95. Ó2013 AACR.

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Section: Discussionsupporting

confidence: 93%

Section: Discussioncontrasting

confidence: 93%

Spontaneous Peripheral T-cell Responses toward the Tumor-Associated Antigen Cyclin D1 in Patients with Clear Cell Renal Cell Carcinoma

Dannenmann

Hermanns

Bransi

et al. 2013

Cancer Immunology Research

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“…This approach discloses the complex nature of cancer cells and leads to identification of genes of which expression patterns are different in tumors when compared with the patterns in nontransformed cells (19). Because TAAs should theoretically be expressed excessively and preferentially by the tumor cells but not by the normal tissues, gene expression profiling with cDNA microarray technologies is useful to identify TAAs (20,21). We analyzed the expression profiles of the newly identified genes with a genome-wide cDNA microarray technology, selected TAA candidates from these genes with the information, and examined whether they contain antigenic T-cell epitope peptides to prove that they are indeed TAAs.…”

Section: It Has Been Demonstrated That Cd8mentioning

confidence: 99%

Ring Finger Protein 43 as a New Target for Cancer Immunotherapy

Uchida

Tsunoda

Wada

et al. 2004

Clinical Cancer Research

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We have performed genome-wide exploration by using cDNA microarray profiling, and successfully identified a new tumor-associated antigen (TAA) that can induce potent cytotoxic T lymphocytes (CTLs) specific to tumor cells. In our preceding study, we identified multiple new genes by using gene expression profiling with a genome-wide cDNA microarray containing 23,040 genes. Among them, we selected RNF43 (ring finger protein 43) as a promising candidate for a TAA expressed by colon cancer cells. In this study, we examined whether the RNF43 protein contains antigenic epitope peptides restricted to HLA-A*0201 or HLA-A*2402. The CTL clones were successfully induced with stimulation by using the peptides binding to HLA-A*0201 (ALWPWLLMA and ALWPWLLMAT) and HLA-A*2402 (NSQPVWLCL), and these CTL clones showed the cytotoxic activity specific to not only the peptide-pulsed targets but also the tumor cells expressing RNF43 and respective HLAs. Lytic activities mediated by two HLA-A2-restricted epitopes were marginal, whereas tumor lysis mediated by the HLA-A24 epitope was clearly better. These findings might be caused by the poor natural presentation of RNF43-11(IX) and RNF43-11(X) by tumors or poor T-cell receptor avidity for these specific epitopes. These results strongly suggest that RNF43 is a new TAA of colon cancer. Furthermore, these results also suggest that our strategy might be a promising one to efficiently discover clinically useful TAAs.

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“…In this report, the peptide vaccine elicited cytotoxic immunity against a variety of cancer cells expressing endogenous adipophilin such as renal cell carcinoma, breast cancer, melanoma, and multiple myeloma etc. [73]. However it remained obscure whether the induced cytotoxic immunity targeted the adipocyte as well, or whether the immunity contributed the antitumor effects if this was the case.…”

Section: Other Vaccines Targeting Cancer Microenvironmentmentioning

confidence: 99%

Cancer Microenvironment and Cancer Vaccine

Ding¹,

Zou²,

Wei³

2012

Cancer Microenvironment

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The cancer microenvironment is constituted of non-transformed host stromal cells such as endothelial cells, fibroblasts, various immune cells, and a complex extracellular matrix secreted by both the normal and neoplastic cells embedded in it. The importance of the microenvironment and its potential in cancer therapy is just being established. Among modalities that target the microenvironment, cancer vaccine is a unique strategy which is aimed to elicit specific immunity against components in the microenvironment. Most, if not all, components can be targeted by the vaccines. The most extensively studied are the endothelial cells, fibroblasts and macrophages as well as ECM. Vaccines are in development for each of them. All the vaccines were proved to be effective at providing protective or therapeutic anti-tumor effects in the pre-clinical models. A few of them have been tested in the clinical trials. The mechanisms of the vaccines were mainly related to the cellular immune response such as CD8+ cytotoxic T cells, and in some instances CD4+ Th cells were involved as well. The present review also discussed the hurdles associated with the microenvironment-based vaccines such as the selection of suitable patients with appropriate biomarkers. With the rapid increase of our knowledge in the cancer microenvironment, the proof-of-concept of microenvironment-based cancer vaccines will surely expand our armamentarium against cancer.

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Induction of Adipophilin-Specific Cytotoxic T Lymphocytes Using a Novel HLA-A2-Binding Peptide That Mediates Tumor Cell Lysis

Abstract: ABSTRACT

Cited by 59 publications

References 19 publications

Spontaneous Peripheral T-cell Responses toward the Tumor-Associated Antigen Cyclin D1 in Patients with Clear Cell Renal Cell Carcinoma

Spontaneous Peripheral T-cell Responses toward the Tumor-Associated Antigen Cyclin D1 in Patients with Clear Cell Renal Cell Carcinoma

Ring Finger Protein 43 as a New Target for Cancer Immunotherapy

Cancer Microenvironment and Cancer Vaccine

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