Recombinant vaccinia/fowlpox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients

Jäger, Elke; Karbach, Julia; Gnjatic, Sacha; Neumann, Antje; Bender, Armin; Valmori, Danila; Ayyoub, Maha; Ritter, Erika; Ritter, Gerd; Jäger, Dirk; Panicali, Dennis; Hoffman, Eric W.; Pan, Linda; Oettgen, Herbert F.; Old, Lloyd J.; Knuth, Alexander

doi:10.1073/pnas.0606512103

Cited by 202 publications

(154 citation statements)

References 26 publications

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“…Moreover, there is compelling evidence demonstrating in both animals and humans that tumors are able to provoke adaptive anti-tumor immune responses mediated by B cells and CD4+ and CD8+ T cells and to initiate innate immune responses mediated by NK or NKT cells [6][7][8][9][10][11][12]. For example, the tumor-associated antigens NY-ESO-1 and LAGE-1 have been shown to be expressed on epithelial ovarian cancers and have been used in tumor vaccines to induce both anti-tumor antibody and tumor-specific CD4+ and CD8+ T cell responses in patients with ovarian cancer [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

T Cells and Stromal Fibroblasts in Human Tumor Microenvironments Represent Potential Therapeutic Targets

Barnas

Simpson-Abelson

Yokota

et al. 2010

Cancer Microenvironment

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The immune system of cancer patients recognizes tumor-associated antigens expressed on solid tumors and these antigens are able to induce tumor-specific humoral and cellular immune responses. Diverse immunotherapeutic strategies have been used in an attempt to enhance both antibody and T cell responses to tumors. While several tumor vaccination strategies significantly increase the number of tumor-specific lymphocytes in the blood of cancer patients, most vaccinated patients ultimately experience tumor progression. CD4+ and CD8+ T cells with an effector memory phenotype infiltrate human tumor microenvironments, but most are hyporesponsive to stimulation via the T cell receptor (TCR) and CD28 under conditions that activate memory T cells derived from the peripheral blood of the cancer patients or normal donors. Attempts to identify cells and molecules responsible for the TCR signaling arrest of tumor-infiltrating T cells have focused largely upon the immunosuppressive effects of tumor cells, tolerogenic dendritic cells and regulatory T cells. Here we review potential mechanisms by which human T cell function is arrested in the tumor microenvironment with a focus on the immunomodulatory effects of stromal fibroblasts. Determining in vivo which cells and molecules are responsible for the TCR arrest in human tumor-infiltrating T cells will be necessary to formulate and test strategies to prevent or reverse the signaling arrest of the human T cells in situ for a more effective design of tumor vaccines. These questions are now addressable using novel human xenograft models of tumor microenvironments.

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Section: Introductionmentioning

confidence: 99%

T Cells and Stromal Fibroblasts in Human Tumor Microenvironments Represent Potential Therapeutic Targets

Barnas

Simpson-Abelson

Yokota

et al. 2010

Cancer Microenvironment

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“…This combination of restricted normal tissue expression, spontaneous immunogenicity and frequent tumor expression has pushed MAGE and NY-ESO-1 to the forefront of tumor immunotherapy as attractive targets for cancer vaccines, 1,8 and multiple clinical trials using these 2 antigens have been carried out, with promising results observed in some studies. [9][10][11][12][13][14][15][16][17] Following the initial identification of MAGE and NY-ESO-1 families, more than 80 gene or gene families have been described as CT or CT candidate genes in the literature. These genes have been organized and annotated into a CT database by the Ludwig Institute for Cancer Research (http://www.cancerimmunity.org/ Ctdatabase/ and http://www.cta.lncc.br).…”

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confidence: 99%

Cancer/testis antigen CT45: Analysis of mRNA and protein expression in human cancer

Chen

Hsu

Lee

et al. 2009

Intl Journal of Cancer

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CT45 is a cancer/testis gene that we previously identified by massively parallel signature sequencing. Encoded by a multigene family on chromosome X, CT45 showed restricted mRNA expression to normal testis and various cancers. In this study, monoclonal antibodies were generated against recombinant CT45 protein, and CT45 protein expression in normal and tumor tissues was evaluated by immunohistochemical analysis. In adult normal tissue, CT45 expression was restricted to testicular germ cells, detected as a nuclear protein mainly at the stage of primary spermatocytes. In tumors, CT45 protein expression correlated with the mRNA levels detected by quantitative RT-PCR, and most lung cancer and ovarian cancers with CT45 mRNA at levels >1% of testicular expression were CT45 protein-positive. In positive cases, CT45 showed expression patterns that ranged from diffuse strong staining to heterogeneous and patchy expression. In lung cancer, CT45 expression was least frequent in adenocarcinoma, more frequent in squamous cell carcinoma and neuroendocrine tumors. Using tissue microarrays, 376 lung cancer, 219 ovarian cancer and 155 breast cancer were evaluated for CT45 protein expression. The expression frequency was highest in ovarian cancer (37%), followed by lung cancer (13%) and lowest in breast cancer (<5%). Given the focal nature of CT45 expression in many cases, these numbers represented the minimal frequency of expression in these tumor types. In summary, the expression frequency and characteristics of CT45 expression are similar to other CT cancer vaccine targets currently in clinical trials, e.g., NY-ESO-1 and MAGE-A, suggesting CT45 as a potentially useful cancer target. ' 2009 UICC

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“…Essentially similar findings were obtained by studies using other preparations of NY-ESO-1 protein vaccine. 11,12,15 …”

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confidence: 99%

“…of the antigen with various adjuvants. [6][7][8][9][10][11][12][13][14] These studies established the safety of the NY-ESO-1 vaccine and demonstrated its immunogenicity.…”

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confidence: 99%

“…Essentially similar findings were obtained by studies using other preparations of NY-ESO-1 protein vaccine. 11,12,15 CD8 T-cells induced by immunization with NY-ESO-1 class I short epitope peptides have been shown to be of low affinity and do not recognize naturally processed NY-ESO-1 on tumor cells. 16 However, the advantage of synthetic long peptides over short peptides for use as vaccines has been reported.…”

mentioning

confidence: 99%

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Induction of CD8 T‐cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20‐mer NY‐ESO‐1f (NY‐ESO‐1 91‐110) peptide

Eikawa

Kakimi

Isobe

et al. 2012

Intl Journal of Cancer

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Immunogenicity of a long 20-mer NY-ESO-1f peptide vaccine was evaluated in a lung cancer patient TK-f01, immunized with the peptide with Picibanil OK-432 and Montanide ISA-51. We showed that internalization of the peptide was necessary to present CD8 T-cell epitopes on APC, contrasting with the direct presentation of the short epitope. CD8 T-cell responses restricted to all five HLA class I alleles were induced in the patient after the peptide vaccination. Clonal analysis showed that B*35:01 and B*52:01-restricted CD8 T-cell responses were the two dominant responses. The minimal epitopes recognized by A*24:02, B*35:01, B*52:01 and C*12:02-restricted CD8 T-cell clones were defined and peptide/HLA tetramers were produced. NY-ESO-1 91-101 on A*24:02, NY-ESO-1 92-102 on B*35:01, NY-ESO-1 96-104 on B*52:01 and NY-ESO-1 96-104 on C*12:02 were new epitopes first defined in this study. Identification of the A*24:02 epitope is highly relevant for studying the Japanese population because of its high expression frequency (60%). High affinity CD8 T-cells recognizing tumor cells naturally expressing the epitopes and matched HLA were induced at a significant level. The findings suggest the usefulness of a long 20-mer NY-ESO-1f peptide harboring multiple CD8 T-cell epitopes as an NY-ESO-1 vaccine. Characterization of CD8 T-cell responses in immunomonitoring using peptide/HLA tetramers revealed that multiple CD8 T-cell responses comprised the dominant response.The NY-ESO-1 antigen was originally identified in esophageal cancer by serological expression cloning (SEREX) using autologous patient serum. 1,2 NY-ESO-1 expression is observed in a wide range of human malignancies, but the expression is restricted to germ cells in the testes in normal adult tissues. [1][2][3][4] Therefore, NY-ESO-1 has emerged as a prototype of a class of cancer/testis (CT) antigens. 5 The efficacy of the NY-ESO-1 antigen as a cancer vaccine has been studied extensively using various preparations, e.g., peptide, protein or DNA, etc. of the antigen with various adjuvants. [6][7][8][9][10][11][12][13][14] These studies established the safety of the NY-ESO-1 vaccine and demonstrated its immunogenicity.In a phase I clinical trial, we immunized cancer patients with a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 whole protein (CHP-NY-ESO-1) and showed that the vaccine had potent capacity to induce the NY-ESO-1 antibody in vaccinated patients. 13,14 The most dominant serological antigenic epitope was NY-ESO-1 91-108. The CHP-NY-ESO-1 vaccine also elicited CD4 and CD8 T-cell responses in immunized patients. 14 Analysis of T cell responses against overlapping peptides (OLPs) spanning the NY-ESO-1 molecule revealed that two dominant NY-ESO-1 regions, regions II (73-114) and III (121-144), were recognized by either CD4 or CD8 T-cells in most patients irrespective of their HLA type. Essentially similar findings were obtained by studies using other preparations of NY-ESO-1 protein vaccine. 11,12,15

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Recombinant vaccinia/fowlpox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients

Cited by 202 publications

References 26 publications

T Cells and Stromal Fibroblasts in Human Tumor Microenvironments Represent Potential Therapeutic Targets

T Cells and Stromal Fibroblasts in Human Tumor Microenvironments Represent Potential Therapeutic Targets

Cancer/testis antigen CT45: Analysis of mRNA and protein expression in human cancer

Induction of CD8 T‐cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20‐mer NY‐ESO‐1f (NY‐ESO‐1 91‐110) peptide

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