Identification and Characterization of a T-Helper Peptide from Carcinoembryonic Antigen

Ruiz, Marta; Kobayashi, Hiroya; Lasarte, Juan José; Prieto, Jesús; Borrás‐Cuesta, Francisco; Celis, Esteban; Sarobe, Pablo

doi:10.1158/1078-0432.ccr-03-0476

Cited by 14 publications

(6 citation statements)

References 40 publications

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“…Th2 immunity) to CEA relative to normal healthy controls [40]. In our study, some important CEA HLA-DR epitopes reported in previous studies [41] may have been overlooked because the basis of our discovery process was elevated IFNγ (i.e. Th1) immunity.…”

Section: Discussionmentioning

confidence: 71%

Identification of a broad coverage HLA-DR degenerate epitope pool derived from carcinoembryonic antigen

Karyampudi

Krco

Kalli

et al. 2009

Cancer Immunol Immunother

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CD4 T cells are important for anti-tumor immune responses. Aside from their role in the activation of CD8 T cells, CD4 T cells also mediate anti-tumor immune responses by recruiting innate immune effectors into the tumor microenvironment. Thus, the search for strategies to boost CD4 T cell immunity is an active area of research. Our goal in this study was to identify HLA-DR epitopes of carcinoembryonic antigen (CEA), a commonly over-expressed tumor antigen. HLA-DR epitopes of CEA were identified using the epitope prediction program, PIC (predicted IC50) and tested using in vitro HLA-DR binding assays. Following CEA epitope confirmation, IFN-γ ELIspot assays were used to detect existing immunity against the HLA-DR epitope panel of CEA in breast and ovarian cancer patients. In vitro generated peptide-specific CD4 T cells were used to determine whether the epitopes are naturally processed from CEA protein. Forty-three epitopes of CEA were predicted, 15 of which had high binding affinity for 8 or more common HLA-DR molecules. A degenerate pool of four, HLA-DR restricted 15-amino acid epitopes (CEA.24, CEA.176/354, CEA.488 and CEA.653) consisting of two novel epitopes (CEA.24 and CEA.488) was identified against which 40% of breast and ovarian cancer patients had pre-existent T cell immunity. All four epitopes are naturally processed by antigen-presenting cells. Hardy-Weinberg analysis showed that the pool is useful in ~94% of patients. Patients with breast or ovarian cancer demonstrate pre-existent immune responses to the tumor antigen CEA. The degenerate pool of CEA peptides may be useful for augmenting CD4 T cell immunity.

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Section: Discussionmentioning

confidence: 71%

Identification of a broad coverage HLA-DR degenerate epitope pool derived from carcinoembryonic antigen

Karyampudi

Krco

Kalli

et al. 2009

Cancer Immunol Immunother

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“…The first possibility is most likely for CEA because the Th cells identified were reactive with the purified antigen, and predictions using a web-based algorithm 3 indicate that many of the CEA peptides that stimulate Th cell responses show high affinity for common MHC class II molecules. Previous studies (27,28,30,31) of Th cells reactive with epitopes on CEA did not address ignorance as a mechanism of tolerance because they did not determine whether the responsive population had previously been activated in vivo. Here, we characterize CEA-specific Th cells that mediate proliferation with primary kinetics and express the CD45RA isoform that is characteristic of naive or quiescent Th cells (33,34) and which have therefore remained ignorant in vivo despite the presence of antigen.…”

Section: Discussionmentioning

confidence: 99%

Different Forms of Helper Tolerance to Carcinoembryonic Antigen: Ignorance and Regulation

Pickford

Watson²,

Barker³

2007

Clinical Cancer Research

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Purpose: Understanding the mechanisms of immune tolerance to tumor-associated antigens (TAA) is an important step in the design of cancer immunotherapy. The aim was to determine how T helper (Th) cell tolerance is mediated for a prototypic TAA, carcinoembryonic antigen (CEA). Experimental Design: Peripheral blood mononuclear cells from 50 healthy volunteers were stimulated with CEA, and the type and fine specificity of any Th cell responses were identified.

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“…Therefore, several techniques have been developed to help stimulate a stronger and more durable immune response. These include the use of multiple peptides in a single vaccine, and the addition of immune stimulatory adjuvants such as helper peptides, molecules to help induce the MHC‐I CD4 T‐cell (TH2)–mediated response,85 and cytokines to help break tolerance 86. Although these peptide vaccines plus adjuvant cocktails have been found to often elicit strong cytotoxic T‐cell responses measured by tetramers and ELISPOT, rarely has tumor regression coincided with this response 82.…”

Section: Melanoma Vaccinesmentioning

confidence: 99%

Melanoma Immunotherapy

Sivendran

Glodny

Pan

et al. 2010

Mount Sinai J Medicine

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Melanoma immunotherapy has been an area of intense research for decades, and this work is now yielding more tangible results for patients. Work has focused on 4 main areas: cytokine therapy, administration of immune-modulating antibodies, adoptive T-cell therapy, and vaccines. Cytokine therapy is an established treatment for advanced melanoma, and immune-modulating antibodies have recently emerged as an exciting new area of drug development with efficacy now established in a phase III trial. Adoptive T-cell therapy provides the proof of principle that T cells can attack and eliminate tumors. It has been challenging, however, to adapt this treatment for widespread use. Vaccines have generally yielded poor results, but intratumor pathogen-based strategies have shown encouraging results in recent trials, perhaps due to stronger immune stimulation. A review of the field of melanoma immunotherapy is provided here, with emphasis on those agents that have reached clinical testing. Novel strategies to induce the immune system to attack melanomas are reviewed. In the future, it is envisioned that immunotherapy will have further application in combination with cytotoxic and targeted therapies.

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Identification and Characterization of a T-Helper Peptide from Carcinoembryonic Antigen

Cited by 14 publications

References 40 publications

Identification of a broad coverage HLA-DR degenerate epitope pool derived from carcinoembryonic antigen

Identification of a broad coverage HLA-DR degenerate epitope pool derived from carcinoembryonic antigen

Different Forms of Helper Tolerance to Carcinoembryonic Antigen: Ignorance and Regulation

Melanoma Immunotherapy

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