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

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

doi:10.1158/0008-5472.can-07-1346

Cited by 128 publications

(111 citation statements)

References 35 publications

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“…Its best-known functions are the retinol conversion to retinoic acid and the oxidation of toxic aldehyde metabo¬lites, such as those formed during the alcohol metabolism and certain chemotherapeutic drugs (eg, cyclophosphamide and cisplatin) (Bosron et al, 1988;Thomasson et al, 1991;Visus et al, 2007). In cancer, ALDH+ cells were identified in the breast and the brain (Ginestier et al, 2007;Rasper et al, 2010).…”

Section: Methods Of Identification Of Cancer Stem Cellsmentioning

confidence: 99%

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

Satpute

Hazarey²,

Ahmed³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Research indicates that a small population of cancer cells is highly tumorigenic, endowed with the capacity for self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells are considered the ''drivers'' of the tumorigenic process in some tumor types, and have been named cancer stem cells (CSC). Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to the acquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype that may contribute to tumor recurrence and metastasis. CSC have been identified in human head and neck squamous cell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase (ALDH) activity. Head and neck cancer stem cells reside primarily in perivascular niches in the invasive fronts where endothelial-cell initiated events contribute to their survival and function. Clinically, CSC enrichment has been shown to be enhanced in recurrent disease, treatment failure and metastasis. CSC represent a novel target of study given their slow growth and innate mechanisms conferring treatment resistance. Further understanding of their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomes in patients with HNSCC. Here, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells, with a focus on the impact of these cells on head and neck tumor progression, metastasis and recurrence due to treatment failure.

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Section: Methods Of Identification Of Cancer Stem Cellsmentioning

confidence: 99%

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

Satpute

Hazarey²,

Ahmed³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…The ALDEFLUOR assay is a fluorescent reagent system, which uses the activity of the detoxifying enzyme aldehyde dehydrogenase (ALDH) to identify and isolate ALDH-expressing cells. It was originally used for the isolation of hematopoietic stem cells (Cheung et al 2007) and is now commonly used for the isolation of CSCs from many cancers, including lung, liver, bone, colon, pancreatic, prostate, head and neck, bladder, thyroid, brain, melanoma, and cervical (Visus et al 2007, Matsui et al 2008, Charafe-Jauffret et al 2010. A growing body of evidence suggests that ALDH activity is a common CSC marker.…”

Section: Thyroid Csc Biomarkersmentioning

confidence: 99%

Cancer stem-like cells and thyroid cancer

Guo¹,

Hardin²,

Lloyd³

2014

Endocrine Related Cancer

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Thyroid cancer is one of the most rapidly increasing malignancies. The reasons for this increase is not completely known, but increases in the diagnosis of papillary thyroid microcarcinomas and follicular variant of papillary thyroid carcinomas along with the enhanced detection of well-differentiated thyroid carcinomas are probably all contributing factors. Although most cases of well-differentiated thyroid carcinomas are associated with an excellent prognosis, a small percentage of patients with well-differentiated thyroid carcinomas as well as most patients with poorly differentiated and anaplastic thyroid carcinomas have recurrent and/or metastatic disease that is often fatal. The cancer stem-like cell (CSC) model suggests that a small number of cells within a cancer, known as CSCs, are responsible for resistance to chemotherapy and radiation therapy, as well as for recurrent and metastatic disease. This review discusses current studies about thyroid CSCs, the processes of epithelial-to-mesenchymal transition (EMT), and mesenchymal-to-epithelial transition that provide plasticity to CSC growth, in addition to the role of microRNAs in CSC development and regulation. Understanding the biology of CSCs, EMT and the metastatic cascade should lead to the design of more rational targeted therapies for highly aggressive and fatal thyroid cancers.

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“…Thus immuno-targeting of melanoma ALDH1A1 positive cells should not be toxic. 19 In our clinical trials, we have applied 30 000 vaccine doses so far, and we did not see any systemic adverse events related to the treatment.…”

Section: Discussionmentioning

confidence: 81%

“…19 have demonstrated that AHDL1A1 88-96 peptide is naturally presented, HLA-A2 restricted and CD8 + T cell defined antigen expressed in squamous cell carcinoma of the head and neck. Using tumor-specific CD8 + T cells, they identified ALDH1A1 as a novel tumor antigen.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, HLA-A2-restricted, AHDL1A1 88-96 -specific CD8 + T cells were detected in the circulation of head and neck squamous cell carcinoma patients. 19 In addition, Taylor et al demonstrated that high ALDH1 expression correlated with better prognosis in melanoma. 24 Interestingly, normal stem cells for example hematopoietic stem cells also express ALDH1A1, but at the lower level than tumor cells.…”

Section: Discussionmentioning

confidence: 99%

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Whole cell melanoma vaccine genetically modified to stem cells like phenotype generates specific immune responses to ALDH1A1 and long-term survival in advanced melanoma patients

Kwiatkowska-Borowczyk

Czerwińska

Mackiewicz

et al. 2018

OncoImmunology

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Allogeneic whole cell gene modified therapeutic melanoma vaccine (AGI-101H) comprising of two melanoma cell lines transduced with cDNA encoding fusion protein composed of IL-6 linked with the soluble IL-6 receptor (sIL-6R), referred to as H6 was developed. H6 served as a molecular adjuvant, however, it has altered vaccine cells phenotype towards melanoma stem cells (MSC)-like with high activity of aldehyde dehydrogenase isoenzyme (ALDH1A1). AGI-101H was applied in advanced melanoma patients with non-resected and resected disease. In the adjuvant setting, it was combined with surgery in case of recurring metastases, which were surgically removed and vaccination continued. A significant fraction of AGI-101H treated melanoma patients is still alive (11–19 years). Out of 106 living patients, 39 were HLA-A2 positive and were the subject of the study. Immunization of melanoma patients resulted in the generation of cytotoxic CD8+ T cells specific for ALDH1A1, which were detected in circulation by HLA-A0201 MHC dextramers loaded with ALDH1A188-96(LLYKLADLI) peptide. Phenotypically they were central memory CD8+ T cells. Re-stimulation with ALDH1A188-96 ex vivo resulted in IFN-γ secretion and cells degranulation. Following each vaccine dose administration, the number of ALDH1A1-CD8+ T cells increased in circulation and returned to the previous level until next dose injection (one month). ALDH1A1-CD8+ T cells were also found, however in the lower number than in vaccinated patients, in the circulation of untreated melanoma with stage IV but were not found in stage II or III and healthy donors. Specific anti-ALDH1 antibodies were present in treated patients. Long-term survival suggests immuno-targeting of MSC in treated patients.

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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

Cited by 128 publications

References 35 publications

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

Cancer stem-like cells and thyroid cancer

Whole cell melanoma vaccine genetically modified to stem cells like phenotype generates specific immune responses to ALDH1A1 and long-term survival in advanced melanoma patients

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