NY‐ESO‐1/LAGE‐1 coexpression with MAGE‐A cancer/testis antigens: A tissue microarray study

Bolli, Martin; Schultz‐Thater, Elke; Zajac, Paul; Güller, Ulrich; Feder, Chantal; Sanguedolce, Francesca; Carafa, Vincenza; Terracciano, Luigi; Hudolin, Tvrtko; Spagnoli, Giulio C.; Tornillo, Luigi

doi:10.1002/ijc.20953

Cited by 55 publications

(53 citation statements)

References 19 publications

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“…Most tumors expressed more than one TAA, which has been described for other tumor entities (16)(17)(18), and which enables therapeutic-targeting of multiple antigens at the same time.…”

Section: Discussionmentioning

confidence: 99%

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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“…Most tumors expressed more than one TAA, which has been described for other tumor entities (16)(17)(18), and which enables therapeutic-targeting of multiple antigens at the same time.…”

Section: Discussionmentioning

confidence: 99%

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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“…15 Briefly, 2 ml of the FliTrx library was induced in the presence of IMC medium containing ampicillin and 100 lg/ml tryptophan at 25 C. Bacteria were then ''panned'' on 60-mm tissue culture plates (Becton Dickinson, Franklin Lakes, NJ) pretreated with the mAb under investigation (50 lg/ml in sterile water). After the removal of unbound cells, bacteria were amplified o/n in IMC medium at 25 C. After five rounds of panning and culture, E. coli were streaked onto RMG medium plates containing 100 lg/ml ampicillin and incubated overnight at 30 C. Individual clones tested positive in Western blot 7 were selected and amplified o/n at 30 C in RM medium containing ampicillin.…”

Section: Epitope Mappingmentioning

confidence: 99%

MAGE‐A10 is a nuclear protein frequently expressed in high percentages of tumor cells in lung, skin and urothelial malignancies

Schultz‐Thater

Piscuoglio

Iezzi

et al. 2011

Intl Journal of Cancer

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MAGE‐A10 is a highly immunogenic member of the MAGE‐A family of cancer/testis tumor‐associated antigens (C/T TAAs). Studies performed with broadly reactive antibodies have helped to initially characterize this TAA. However, no specific reagents have been developed so far, thus preventing a thorough analysis of its expression in healthy and tumoral tissues. We have produced MAGE‐A10 gene product in soluble recombinant form, and we have used it to generate specific monoclonal antibodies (mAbs). One of these reagents, recognizing an epitope located at the COOH terminus of the MAGE‐A10 gene product, was used to stain a multitumor tissue microarray comprising more than 2,500 paraffin‐embedded specimens including healthy tissues, benign tumors and malignancies of different histological origin. MAGE‐A10 protein was identified as an intranuclear protein of an apparent molecular weight of 70 kDa, expressed in normal spermatogonia and spermatocytes but in no other healthy tissue. Most importantly, this C/T TAA appears to be expressed in high (>50%) percentages of cancer cells from a number of malignancies, including lung, skin and urothelial tumors. Unexpectedly, high expression of MAGE‐A10 TAA at the protein level was also detectable in gynecological malignancies and stomach and gall bladder cancers. The characterization of MAGE‐A10‐specific reagents might set the stage for the development of targeted active immunotherapy by clarifying potential indications and by allowing the selection of patients eligible for treatment and the monitoring of its effectiveness.

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“…This mAb is originally raised against Mage-3, 31 but observed to preferentially stain Mage-4 in tissue sections 32 ; however, cross-reactivity to other Mage-A antigens have been described. 33 …”

Section: Expression Of Tumor Antigens In Seminoma Lesionsmentioning

confidence: 99%

Tumor infiltrating lymphocytes in seminoma lesions comprise clonally expanded cytotoxic T cells

Hadrup

Brændstrup

Jacobsen

et al. 2006

Intl Journal of Cancer

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Seminoma lesions are characterized by a brisk inflammatory infiltrate containing both CD4 and CD8 T cells, which is of prognostic significance. However, whether seminoma cells express the HLA molecules required for classical T-cell recognition remains controversial. In the present study, we conducted a molecular, phenotypical and functional characterization of tumor infiltrating lymphocytes (TILs) from seminoma lesions. T-cell receptor clonotype mapping demonstrated the presence of clonally expanded T cells in the majority of the lesions. The cytotoxic capacity of TILs was indicated by expression of CD107a, which is a recently described surrogate marker for cytolytic activity. Indeed, the frequency of CD107a positive cells was substantially higher in TILs when compared to peripheral blood mononuclear cells. Moreover, fluorescence activated cell sorting of CD107a positive TILs allowed comparison of the clonotypic T-cell receptor fingerprint and demonstrated the ability of expanded clones to express this cytotoxic marker, suggesting cytotoxic activity at the tumor site. The cytotoxicity was confirmed by in situ granzyme B expression. Furthermore, by staining with multimeric HLA-peptide complexes, we could demonstrate the presence of Mage-3 specific T cells among TILs. In summary, specific and functional T-cell responses are operative in seminoma, indicating that the inflammatory infiltrate is indeed involved in the immunological control of the tumor. ' 2006 Wiley-Liss, Inc.

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NY‐ESO‐1/LAGE‐1 coexpression with MAGE‐A cancer/testis antigens: A tissue microarray study

Cited by 55 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

MAGE‐A10 is a nuclear protein frequently expressed in high percentages of tumor cells in lung, skin and urothelial malignancies

Tumor infiltrating lymphocytes in seminoma lesions comprise clonally expanded cytotoxic T cells

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