Identification of Five New HLA-B*3501-Restricted Epitopes Derived from Common Melanoma-Associated Antigens, Spontaneously Recognized by Tumor-Infiltrating Lymphocytes

Benlalam, Houssem; Linard, Boris; Guilloux, Yannick; Moreau-Aubry, Agnès; Derré, Laurent; Viles, Elisabeth; Dréno, Brigitte; Jotereau, Francine; Labarrière, Nathalie

doi:10.4049/jimmunol.171.11.6283

Cited by 50 publications

(33 citation statements)

References 33 publications

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“…74 Most of the work to date with respect to HLA class Irestricted responses has been in the context of HLA-A2. Epitopes restricted by other class I alleles have now been detected for HLA-B35, 75 HLA-B51 76 and Cw3. HLA class II, DQ 77 multiple DR alleles have been found stimulating both Th1 and Th2 responses (Tables 2-4).…”

Section: T-cell Responsesmentioning

confidence: 99%

Directions in the immune targeting of cancer: Lessons learned from the cancer‐testis Ag NY‐ESO‐1

et al. 2006

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Summary Since the early 1990s, numerous cancer Ag have been defined and for a handful of these there is now some clinical experience, which has made it possible to assess their value as targets for cancer immunotherapy. The cancer-testis Ag have been particularly attractive because their expression is limited to cancer and virtually no nonmalignant cells apart from germ cells and trophoblast. Among these, NY-ESO-1 has been the focus of our attention. The exceptional immunogenicity of this Ag coupled with its widespread distribution among many cancer types make it a very good vaccine candidate, with the potential to be used in vaccines against many types of malignancies. This article reviews emerging knowledge about the biology of NY-ESO-1 and experience with the early clinical development of vaccines directed against NY-ESO-1. These early studies have yielded a wealth of information about the immunology of NY-ESO-1 and set the scene for future clinical strategies for immune targeting of cancer.Key words: cancer immunology, cancer-testis Ag, cancer vaccine, dendritic cell, ISCOMATRIX, NY-ESO-1. Biology of NY-ESO-1NY-ESO-1 was first discovered using 'SERological identification of antigens by recombinant EXpression cloning' (SEREX). This is a method used for identifying the antibody repertoire of cancer-bearing patients by screening their serum against an expression library that typically displays protein Ag derived from a cancer source such as an autologous tumour or a cell line. In this case, NY-ESO-1 was found by using serum from a patient with squamous cell carcinoma (SCC) of the oesophagus. 1,2 Expression of NY-ESO-1 protein has been shown in multiple cancer types (Table 1), as well as in spermatogonia, oogonia and placenta. 3,4 Although NY-ESO-1 mRNA expression has been detected at low levels in some other normal tissues, it is unclear whether this is significant in the absence of detectable protein. 4,5 Other genes with similar names (NY-ESO-2, -3, -4, -5, -6, -7, -8) have no homology with NY-ESO-1. 2 The NY-ESO-1 gene is located on chromosome Xq28, 1 which carries a disproportionately high number of cancertestis (CT) Ag genes. 6 Up to 10% of the genes on chromosome X are CT Ag genes. The expression of these genes seems to be related to the demethylation of the promoter regions because experimental demethylation leads to the upregulation of CT Ag expression. [7][8][9][10][11][12][13][14][15][16][17][18] The NY-ESO-1 gene encodes a protein of 180 amino acids with M r 18 kDa, 2 which is expressed primarily in the cytoplasm although nuclear expression can be seen in some spermatogonia. 4 A homologue of NY-ESO-1, termed LAGE-1, was identified using representational difference analysis. 14 LAGE-1 and NY-ESO-1 are 84-89% homologous at the protein level. 14 Alternative splicing of LAGE-1 mRNA leads to the expression of two major transcripts encoding proteins of 210 and 180 amino acids, respectively. LAGE-1 is expressed in a wide variety of cancers (Table 1), usually, but not always, in conjunction with NY-ESO-1 or ...

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Section: T-cell Responsesmentioning

confidence: 99%

Directions in the immune targeting of cancer: Lessons learned from the cancer‐testis Ag NY‐ESO‐1

et al. 2006

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“…To evaluate the capability of our approach to clone functional TCRs from antigen-specific T-cell populations of low abundance, we used NY-ESO-1, one of the best characterized members of the cancer/germline antigen family (37). In patients with cancer, NY-ESO-1 frequently elicits spontaneous CD4 þ and CD8 þ T-cell responses (29,38,39), whose specificities have been mapped over the last years (40,41). Because of its natural immunogenicity, it is a prototype for immunotherapy strategies, and many clinical trials targeting NY-ESO-1 by either vaccination or transfer of TCR-engineered T cells are ongoing.…”

Section: Cloning Of Tcrs Directed Against Hla Class I-and Iirestrictementioning

confidence: 99%

Functional TCR Retrieval from Single Antigen-Specific Human T Cells Reveals Multiple Novel Epitopes

Simon

Omokoko

Breitkreuz

et al. 2014

Cancer Immunology Research

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The determination of the epitope specificity of disease-associated T-cell responses is relevant for the development of biomarkers and targeted immunotherapies against cancer, autoimmune, and infectious diseases. The lack of known T-cell epitopes and corresponding T-cell receptors (TCR) for novel antigens hinders the efficient development and monitoring of new therapies. We developed an integrated approach for the systematic retrieval and functional characterization of TCRs from single antigen-reactive T cells that includes the identification of epitope specificity. This is accomplished through the rapid cloning of full-length TCR-a and TCR-b chains directly from single antigen-specific CD8 þ or CD4 þ T lymphocytes. The functional validation of cloned TCRs is conducted using in vitro-transcribed RNA transfer for expression of TCRs in T cells and HLA molecules in antigen-presenting cells. This method avoids the work and bias associated with repetitive cycles of in vitro T-cell stimulation, and enables fast characterization of antigen-specific T-cell responses. We applied this strategy to viral and tumor-associated antigens (TAA), resulting in the retrieval of 56 unique functional antigenspecific TCRs from human CD8 þ and CD4 þ T cells (13 specific for CMV-pp65, 16 specific for the well-known TAA NY-ESO-1, and 27 for the novel TAA TPTE), which are directed against 39 different epitopes. The proof-of-concept studies with TAAs NY-ESO-1 and TPTE revealed multiple novel TCR specificities. Our approach enables the rational development of immunotherapy strategies by providing antigen-specific TCRs and immunogenic epitopes.

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“…2), which was maintained until the end of the vaccination regimen, while no patients in Arm B showed a similar response. Although NY-ESO-1 epitopes contained within the NY-ESO-1 85-102 region were previously shown to be presented in the context of HLA-B35, B51 and Cw3, [14][15][16] patients lacking the expression of HLA-B35, B51 and Cw3, such as patient C002, developed strong CD8…”

Section: /Cd3mentioning

confidence: 99%

NY‐ESO‐1 specific antibody and cellular responses in melanoma patients primed with NY‐ESO‐1 protein in ISCOMATRIX and boosted with recombinant NY‐ESO‐1 fowlpox virus

Chen

Dawoodji

Tarlton

et al. 2014

Intl Journal of Cancer

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Vaccination strategies based on repeated injections of NY-ESO-1 protein formulated in ISCOMATRIX particles (NY-ESO-1 ISCOMATRIX) have shown to elicit combined NY-ESO-1 specific antibody and T cell responses. However, it remains unclear whether heterologous prime-boost strategies based on the combination with NY-ESO-1 ISCOMATRIX with different NY-ESO-1 boosting reagents could be used to increase NY-ESO-1 CD8 1 or CD4 1 T cell responses. To address this question, we carried out a randomized clinical trial in 39 high-risk, resected melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX, and then boosted with repeated injections of either recombinant fowlpox virus encoding full length NY-ESO-1 (rF-NY-ESO-1) (Arm A) or NY-ESO-1 ISCOMATRIX alone (Arm B). We have comprehensively analyzed NY-ESO-1 specific T cells and B cells response in all patients before and after vaccination for a total of seven time points per patient. NY-ESO-1 ISCOMATRIX alone elicited a strong NY-ESO-1 specific CD4 1 T cell and antibody response, which was maintained by both regiments at similar levels. Current vaccination strategies based on the use of recombinant viruses are failing to elicit specific T-cell responses similar to those generated by natural infections. The limited success of recombinant viruses as delivery vectors for T cell vaccines is mainly due to their high immunogenicity, resulting in an overwhelming immune response focused on the viral-vector proteins rather than on the desired recombinant protein antigens. 1 However, it remains unclear whether recombinant viruses can be used to boost the magnitude of immune responses elicited by the prior injection of recombinant immunogenic proteins.The cancer-testis antigen NY-ESO-1 is an attractive target antigen for cancer therapy, as it is expressed in many cancer types, but not normal tissues, except testis.2 Although promising results in various NY-ESO-1 formulations have been reported in recent cancer vaccine studies, 3-6 the optimal strategy for generating integrated antibody and T cell responses to control tumor growth has yet to be determined.ISCOMATRIX adjuvant is comprised of saponin, cholesterol and phospholipid and is capable of associating with proteins to form ISCOMATRIX vaccines.7 Recombinant

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Identification of Five New HLA-B*3501-Restricted Epitopes Derived from Common Melanoma-Associated Antigens, Spontaneously Recognized by Tumor-Infiltrating Lymphocytes

Cited by 50 publications

References 33 publications

Directions in the immune targeting of cancer: Lessons learned from the cancer‐testis Ag NY‐ESO‐1

Directions in the immune targeting of cancer: Lessons learned from the cancer‐testis Ag NY‐ESO‐1

Functional TCR Retrieval from Single Antigen-Specific Human T Cells Reveals Multiple Novel Epitopes

NY‐ESO‐1 specific antibody and cellular responses in melanoma patients primed with NY‐ESO‐1 protein in ISCOMATRIX and boosted with recombinant NY‐ESO‐1 fowlpox virus

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