Cancer vaccines targeting carcinoembryonic antigen: state-of-the-art and future promise

Gameiro, Sofia R.; Jammeh, Momodou L.; Hodge, James W.

doi:10.1586/erv.13.40

Cited by 17 publications

(11 citation statements)

References 78 publications

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“…Our findings strongly support the possibility of the inhibition of metastatic processes in advanced lung cancer by antibodies that target CEA, as a previous preclinical study disclosed 16. A multitude of recently developed CEA cancer vaccines are now in various stages of development and require further study to determine the ultimate roles of these vaccines in cancer treatments 7.…”

Section: Discussionsupporting

confidence: 85%

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Serum Carcinoembryonic Antigen Levels and the Risk of Whole-body Metastatic Potential in Advanced Non-small Cell Lung Cancer

Lee¹,

Kim²,

Kang³

et al. 2014

J. Cancer

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Background: This study aimed to clarify the clinical associations between serum carcinoembryonic antigen (CEA) levels and whole-body metastatic distribution in stage IV NSCLC patients.Methods: This study analyzed 377 eligible patients between June 2007 and December 2012. All patients enrolled in the study were newly diagnosed with stage IV NSCLC and had records of pre-treatment serum CEA levels. The serum CEA levels were categorized as normal (< 5 ng/ml) or abnormal (≥ 5 ng/ml) to reveal clinically correlated factors with abnormal serum CEA levels.Results: The median age of the study cohort was 65 years old (range, 30-94), and 236 (62.6%) patients were male. Two hundred seventy-seven (73.5%) patients had tumors with a histology that is consistent with adenocarcinoma. The median serum CEA value was 8.2 ng/ml (range, 0.1-2872.7), and 218 (57.8%) patients had abnormal serum CEA levels. In multivariate analysis, abnormal serum CEA levels had statistically strong associations with non-squamous cell histology (P=0.002), bone (P=0.001), and brain metastases (P=0.005); and were also closely correlated with positive metastatic LN status (P=0.083) and pulmonary metastasis (P=0.065). Very high serum CEA levels (≥ 100 ng/ml) were additionally correlated with abdominal/pelvic metastasis (P < 0.001).Conclusions: Our findings suggested that abnormal serum CEA levels were strongly correlated with increased whole-body metastatic potential in advanced NSCLC. The results provided evidence for future exploratory anti-CEA targeting and intensive systemic assessment in advanced NSCLC patients with abnormal serum CEA levels.

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Section: Discussionsupporting

confidence: 85%

“…CEA is overexpressed in approximately 70% of cases of non-small cell lung cancer (NSCLC), as well as more than 95% of adenocarcinomas of gastrointestinal origin 7. The clinical usefulness of serum CEA in lung cancer has also been vigorously explored recently 8-12.…”

Section: Introductionmentioning

confidence: 99%

Serum Carcinoembryonic Antigen Levels and the Risk of Whole-body Metastatic Potential in Advanced Non-small Cell Lung Cancer

Lee¹,

Kim²,

Kang³

et al. 2014

J. Cancer

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“…From then on, several different CD8-and CD4-restricted peptide epitopes have been found and used in human immunotherapy [70][71][72][73][74][75]. Licensed CEA-based vaccines are extensively used in many variations of cancer immunotherapy [76]. There is strong evidence supporting the role of anti-CEA T cell responses in breaking immunological tolerance towards other tumour antigens.…”

Section: Identification Of Human Taasmentioning

confidence: 99%

Tumour Immunogenicity, Antigen Presentation, and Immunological Barriers in Cancer Immunotherapy

Escors

2014

New Journal of Science

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Since the beginning of the 20th century, scientists have tried to stimulate the antitumour activities of the immune system to fight against cancer. However, the scientific effort devoted on the development of cancer immunotherapy has not been translated into the expected clinical success. On the contrary, classical antineoplastic treatments such as surgery, radiotherapy, and chemotherapy are the first line of treatment. Nevertheless, there is compelling evidence on the immunogenicity of cancer cells and the capacity of the immune system to expand cancer-specific effector cytotoxic T cells. However, the effective activation of anticancer T cell responses strongly depends on efficient tumour antigen presentation from professional antigen presenting cells such as dendritic cells (DCs). Several strategies have been used to boost DC antigen presenting functions, but at the end cancer immunotherapy is not as effective as would be expected according to preclinical models. In this review, we comment on these discrepancies, focusing our attention on the contribution of regulatory T cells and myeloid-derived suppressor cells to the lack of therapeutic success of DC-based cancer immunotherapy.

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“…Currently there is much interest in targeting CEA via anticancer vaccination or T-cell–directed adoptive transfer ( 14 , 15 ), thus our findings open up debate about the potential risks of such strategies in certain situations. Why should CEA-specific, but not 5T4-specific, responses be detrimental?…”

mentioning

confidence: 96%

Assessing the Prognostic Value of Preoperative Carcinoembryonic Antigen-Specific T-Cell Responses in Colorectal Cancer

Scurr

Brown

Bento

et al. 2015

JNCI: Journal of the National Cancer Institute

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Current dogma suggests that tumor-reactive IFN-γ–producing (TH1-type) T-cells are beneficial to patient outcome; however, the clinical consequence of these responses with respect to long-term prognosis in colorectal cancer (CRC) is not understood. Here, we compared the utility of preoperative, peripheral blood–derived IFN-γ+ T-cell responses specific to carcinoembryonic antigen (CEA), 5T4, or control antigens (n = 64) with tumor staging and clinical details (n = 87) in predicting five-year outcome of CRC patients who underwent resection with curative intent. Although disease recurrence was more likely in patients with stage III tumors, the presence of preoperative, CEA-specific IFN-γ–producing T-cells identified patients at a statistically significantly greater risk of tumor recurrence following surgical resection, irrespective of tumor stage (odds ratio = 5.00, 95% confidence interval = 1.96 to 12.77, two-sided P <.001). Responses to other antigens, including 5T4, did not reflect outcome. Whilst these results initially appear surprising, they could improve prognostication and help redirect adjuvant treatments.

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Cancer vaccines targeting carcinoembryonic antigen: state-of-the-art and future promise

Cited by 17 publications

References 78 publications

Serum Carcinoembryonic Antigen Levels and the Risk of Whole-body Metastatic Potential in Advanced Non-small Cell Lung Cancer

Serum Carcinoembryonic Antigen Levels and the Risk of Whole-body Metastatic Potential in Advanced Non-small Cell Lung Cancer

Tumour Immunogenicity, Antigen Presentation, and Immunological Barriers in Cancer Immunotherapy

Assessing the Prognostic Value of Preoperative Carcinoembryonic Antigen-Specific T-Cell Responses in Colorectal Cancer

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