Identification of human aldehyde dehydrogenase 1 family member A1 as a novel CD8+ T-cell-defined tumor antigen in squamous cell carcinoma of the head and neck.

Identification of human aldehyde dehydrogenase 1 family member A1 as a novel CD8+ T-cell-defined tumor antigen in squamous cell carcinoma of the head and neck. Research Abstract Details 

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Identification of human aldehyde dehydrogenase 1 family member A1 as a novel CD8+ T-cell-defined tumor antigen in squamous cell carcinoma of the head and neck. Abstract Text:

Carmen Visus,Diasuke Ito,Andrew Amoscato,Malgorzata Maciejewska-Franczak,Ahmed Abdelsalem,Rajiv Dhir,Dong M Shin,Vera S Donnenberg,Theresa L Whiteside,Albert B DeLeo,

Few epitopes are available for vaccination therapy of patients with squamous cell carcinoma of the head and neck (SCCHN). Using a tumor-specific CTL, aldehyde dehydrogenase 1 family member A1 (ALDH1A1) was identified as a novel tumor antigen in SCCHN. Mass spectral analysis of peptides in tumor-derived lysates was used to determine that the CTL line recognized the HLA-A*0201 (HLA-A2) binding ALDH1A1(88-96) peptide. Expression of ALDH1A1 in established SCCHN cell lines, normal mucosa, and primary keratinocytes was studied by quantitative reverse transcription-PCR and immunostaining. Protein expression was further defined by immunoblot analysis, whereas ALDH1A1 activity was measured using ALDEFLUOR. ALDH1A1(88-96) peptide was identified as an HLA-A2-restricted, naturally presented, CD8(+) T-cell-defined tumor peptide. ALDH1A1(88-96) peptide-specific CD8(+) T cells recognized only HLA-A2(+) SCCHN cell lines, which overexpressed ALDH1A1, as well as targets transfected with ALDH1A1 cDNA. Target recognition was blocked by anti-HLA class I and anti-HLA-A2 antibodies. SCCHN cell lines overexpressing ALDH1 had high enzymatic activity. ALDH1A1 protein was expressed in 12 of 17 SCCHN, and 30 of 40 dysplastic mucosa samples, but not in normal mucosa. ALDH1A1 expression levels in target cells correlated with their recognition by ALDH1A1(88-96) peptide-specific CD8(+) T cells. Our findings identify ALDH1A1, a metabolic antigen, as a potential target for vaccination therapy in the cohort of SCCHN subjects with tumors overexpressing this protein. A smaller cohort of subjects with SCCHN, whose tumors express little to no ALDH1A1, and thus are deficient in conversion of retinal to retinoic acid, could benefit from chemoprevention therapy.

Identification of human aldehyde dehydrogenase 1 family member A1 as a novel CD8+ T-cell-defined tumor antigen in squamous cell carcinoma of the head and neck. Publishing Authors By Initials

C Visus,D Ito,A Amoscato,M Maciejewska-Franczak,A Abdelsalem,R Dhir,DM Shin,VS Donnenberg,TL Whiteside,AB DeLeo,

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Identification of human aldehyde dehydrogenase 1 family member A1 as a novel CD8+ T-cell-defined tumor antigen in squamous cell carcinoma of the head and neck. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Cancer research

VOLUME: 67

Page Numbers: 10538-45

Journal Abbreviation: Cancer Res.

ISSN: 1538-7445

DAY: 1

MONTH: Nov

YEAR: 2007

Identification of human aldehyde dehydrogenase 1 family member A1 as a novel CD8+ T-cell-defined tumor antigen in squamous cell carcinoma of the head and neck. Information

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LANGUAGE: eng

NlmUniqueID: 2984705

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Grant and Affiliation Information for Identification of human aldehyde dehydrogenase 1 family member A1 as a novel CD8+ T-cell-defined tumor antigen in squamous cell carcinoma of the head and neck.

AFFILIATION: Division of Basic Research, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.

Country: United States

AGENCY: United States NCI

GRANT: P50 CA97190

ACRONYM: CA

MEDLINETA: Cancer Res

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