Induction of CAMEL/NY-ESO-ORF2-specific CD8+ T cells upon stimulation with dendritic cells infected with a modified Ad5 vector expressing a chimeric Ad5/35 fiber

Slager, Elisabeth H.; Minne, Caroline E. van der; Goudsmit, Jaap; Oers, Johanna M.M. van; Kostense, Stefan; Havenga, Menzo; Osanto, Susanne; Griffioen, Marieke

doi:10.1038/sj.cgt.7700674

Cited by 15 publications

(6 citation statements)

References 45 publications

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“…The reason for this may be the lack of expression of the primary receptor for Ad5, CAR (10). In contrast, monocyte-derived DCs, epidermal DCs (e.g., Langerhans cells), and dermal DCs express CD46, the high-affinity receptor for rAd35, and are therefore more easily infected with rAd35 than with rAd5 (28,(35)(36)(37)(38). Here, we show that the distinct DC subsets (primary MDCs and PDCs) isolated directly from blood also lack cell surface CAR expression yet express high levels of CD46.…”

Section: Discussionmentioning

confidence: 79%

Myeloid and Plasmacytoid Dendritic Cells Are Susceptible to Recombinant Adenovirus Vectors and Stimulate Polyfunctional Memory T Cell Responses

Loré

Adams

Havenga

et al. 2007

The Journal of Immunology

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109

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Although replication-incompetent recombinant adenovirus (rAd) type 5 is a potent vaccine vector for stimulating T and B cell responses, high seroprevalence of adenovirus type 5 (Ad5) within human populations may limit its clinical utility. Therefore, alternative adenovirus serotypes have been studied as vaccine vectors. In this study, we characterized the ability of rAd5 and rAd35 to infect and induce maturation of human CD11c+ myeloid dendritic cells (MDCs) and CD123+ plasmacytoid dendritic cells (PDCs), and their ability to stimulate Ag-specific T cells. Both MDCs and PDCs were found to express the primary receptor for Ad35 (CD46) but not Ad5 (coxsackie-adenovirus receptor; CAR). Both dendritic cell (DC) subsets were also more susceptible to rAd35 than to rAd5. MDCs were more susceptible to both rAd35 and rAd5 than were PDCs. Whereas rAd35 used CD46 for entry into DCs, entry of rAd5 may be through a CAR-independent pathway. Exposure to rAd35 but not rAd5 induced high levels of IFN-α in PDCs and phenotypic differentiation in both DC subsets. MDCs and PDCs exposed to either rAd5 or rAd35 encoding for CMV pp65 were able to present pp65 and activate CMV-specific memory CD8+ and CD4+ T cells in a dose-dependent manner, but MDCs stimulated the highest frequencies of pp65-specific T cells. Responding T cells expressed multiple functions including degranulation (CD107a surface mobilization) and production of IFN-γ, IL-2, TNF-α, and MIP-1β. Thus, the ability of rAd35 to naturally target important DC subsets, induce their maturation, and appropriately present Ag to T cells may herald greater in vivo immunogenicity than has been observed with rAd5.

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Section: Discussionmentioning

confidence: 79%

Myeloid and Plasmacytoid Dendritic Cells Are Susceptible to Recombinant Adenovirus Vectors and Stimulate Polyfunctional Memory T Cell Responses

Loré

Adams

Havenga

et al. 2007

The Journal of Immunology

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109

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“…2) rAd5F35 vectors transduce DC in vitro with conserved high efficiency in the presence of primary skin-derived fibroblasts (10). 3) rAd5F35-transduced DC are more potent in vitro CTL activators than rAd5-transduced DC, as shown for melanoma-associated transgene products by the activation of a gp100-specific CTL clone and the induction of CTL-recognized Ag on melanoma-specific and tumor-reactive CD8 ϩ T cells (11). In aggregate, the above listed data clearly indicate the possible utility of Ad35-based vectors for in vivo DC-targeted vaccination approaches.…”

Section: Discussionmentioning

confidence: 82%

“…As a result, MoDC are more efficiently transduced by Ad35-based vectors than by rAd5, without interfering with the DC's activation potential (10). Indeed, MoDC infected with Ad5F35 chimeric vectors have been used successfully to generate antitumor CD8 ϩ T cell responses in vitro (11).…”

Section: Endritic Cells (Dc)mentioning

confidence: 98%

Intradermal Delivery of Adenoviral Type-35 Vectors Leads to High Efficiency Transduction of Mature, CD8+ T Cell-Stimulating Skin-Emigrated Dendritic Cells

Gruijl¹,

Ophorst

Goudsmit

et al. 2006

The Journal of Immunology

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Recombinant adenovirus (Ad) type 35 (rAd35) shows great promise as vaccine carrier with the advantage of low pre-existing immunity in human populations, in contrast to the more commonly used rAd5 vector. The rAd35 vector uses CD46 as a high-affinity receptor, which, unlike the rAd5 receptor, is expressed on human dendritic cells (DC), the most powerful APCs identified to date. In this study, we show that in contrast to rAd5, rAd35 infects migrated and mature CD83+ cutaneous DC with high efficiency (up to 80%), when delivered intradermally in an established human skin explant model. The high transduction efficiency is in line with high expression levels of CD46 detected on migratory cutaneous DC, which proved to be further increased upon intradermal administration of GM-CSF and IL-4. As compared with Ad5, these Ad35 infection characteristics translate into higher absolute numbers of skin-emigrated DC per explant that both express the transgene and are phenotypically mature. Finally, we demonstrate that upon intracutaneous delivery of a rAd35 vaccine encoding the circumsporozoite (CS) protein of Plasmodium falciparum, emigrated DC functionally express and process CS-derived epitopes and are capable of activating specific CD8+ effector T cells, as evidenced by activation of an HLA-A2-restricted CS-specific CD8+ T cell clone. Collectively, these data demonstrate the utility of rAd35 vectors for efficient in vivo human DC transduction.

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“…85 It has recently become apparent that tumour Ag can be derived from both primary and non-primary open reading frames of various genes. [86][87][88][89][90][91][92][93] An alternative open reading frame product of LAGE-1 and NY-ESO-1, termed CAMEL, was shown to contain epitopes that could be recognized by CD8 1 T cells 89 and by CD4 1 T cells 91,92,94 in the context of HLA-A2 and HLA-DR, respectively. Additional HLA-A31-restricted peptides have also been described.…”

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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Induction of CAMEL/NY-ESO-ORF2-specific CD8+ T cells upon stimulation with dendritic cells infected with a modified Ad5 vector expressing a chimeric Ad5/35 fiber

Cited by 15 publications

References 45 publications

Myeloid and Plasmacytoid Dendritic Cells Are Susceptible to Recombinant Adenovirus Vectors and Stimulate Polyfunctional Memory T Cell Responses

Myeloid and Plasmacytoid Dendritic Cells Are Susceptible to Recombinant Adenovirus Vectors and Stimulate Polyfunctional Memory T Cell Responses

Intradermal Delivery of Adenoviral Type-35 Vectors Leads to High Efficiency Transduction of Mature, CD8+ T Cell-Stimulating Skin-Emigrated Dendritic Cells

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

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