T‐cell recognition of melanoma‐associated antigens

Castelli, Chiara; Rivoltini, Licia; Andreola, Giovanna; Carrabba, Matteo Giovanni; Renkvist, Nicolina; Parmiani, Giorgio

doi:10.1002/(sici)1097-4652(200003)182:3<323::aid-jcp2>3.0.co;2-#

Cited by 110 publications

(42 citation statements)

References 56 publications

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“…Most of these antigens have been cloned from melanoma cells 2 and less frequently from other types of cancer. 3,4 For the development of effective immunotherapy against cancer, the identification of a larger variety of tumor-associated antigens is of great importance, to broaden the range of different tumors that can be treated as well as to prevent the outgrowth of antigen-loss tumor cells after vaccination.…”

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confidence: 99%

TCR reconstitution in Jurkat reporter cells facilitates the identification of novel tumor antigens by cDNA expression cloning

Aarnoudse

Krüse

Konopitzky

et al. 2002

Intl Journal of Cancer

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The identification of novel tumor antigens is of extreme importance for effective immunotherapy against cancer. A major obstacle in this field is the limited life span of tumorspecific cytotoxic T lymphocytes (CTLs) in vitro. Therefore we searched for a method to isolate the tumor specificity of these CTLs, i.e., their T-cell receptors (TCRs) and transfer it to an immortalized T-cell line. For this purpose, a TCRnegative Jurkat T-cell line was equipped with a nuclear factor of activated T cells ( Key words: T-cell receptor; tumor antigen; NFAT; CAMEL; cDNA expression cloning; CD8; luciferase; retrovirus; JurkatSince the characterization of the first human tumor-specific antigen in 1991, MAGE-1, 1 a considerable number of other targets for tumor-specific cytotoxic T cells (CTLs) have been identified. Most of these antigens have been cloned from melanoma cells 2 and less frequently from other types of cancer. 3,4 For the development of effective immunotherapy against cancer, the identification of a larger variety of tumor-associated antigens is of great importance, to broaden the range of different tumors that can be treated as well as to prevent the outgrowth of antigen-loss tumor cells after vaccination.Several strategies have led to the identification of tumor-specific T-cell epitopes. Most frequently, cDNA expression cloning has been employed, in which the gene encoding the antigen is identified by transfecting pools of tumor-derived cDNA into recipient cells, followed by screening with the tumor-specific CTL. [5][6][7][8] In another approach, the peptide epitope for the tumor-specific CTL is identified, either by peptide elution and mass spectrometry 9 or by mimicry from designated peptide libraries, 10 although with the latter method no tumor antigens have been identified yet. Several tumor antigens have been found by the method of "reverse immunology." These antigens were initially cloned on the basis of their differential expression in tumors versus healthy tissues and antigenic peptides were subsequently identified by performing in vitro T-cell inductions. 11,12 For efficient elucidation of novel physiologically relevant tumor-specific antigens, large quantities of tumor-specific CTLs are required to allow for multiple screening rounds. In practice, the limited amount of CTLs available often constitutes the major obstacle for the cloning of new tumor antigens. We have sought to circumvent this issue by cloning and transferring the T-cell receptor (TCR) of a tumor-specific T cell to an immortalized T-cell line. In this way, an unlimited source of tumor-specific T cells can be obtained, which facilitates the identification of novel tumor antigens. The feasibility of TCR cloning and transfer has already been demonstrated by others. [13][14][15][16][17] We studied the properties of a TCR, isolated from a characterized CAMEL (CTL-recognized antigen on melanoma)-specific CTL clone, 8 which was transferred into a TCR-negative human leukemia Jurkat T-cell line. To detect TCRmediated activation, the cells were tr...

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confidence: 99%

TCR reconstitution in Jurkat reporter cells facilitates the identification of novel tumor antigens by cDNA expression cloning

Aarnoudse

Krüse

Konopitzky

et al. 2002

Intl Journal of Cancer

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“…This method is based on the detection of antigens within recombinantly expressed tumor cDNA phage libraries by autologous antibodies (21). One variant of the method (22), which has also been applied in the present study, aims directly at the identification of antigens that are expressed solely in tumors and germline cells such as MAGE genes (23,24). Cancer germline genes are expressed only in spermatoids͞spermatogones and in tumors and thus, in view of the fact that the testis is an immunoprivileged site, can be considered immunologically tumorspecific (25,26).…”

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confidence: 99%

Serological detection of cutaneous T-cell lymphoma-associated antigens

Eichmüller¹

2001

Proceedings of the National Academy of Sciences

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Cutaneous T-cell lymphomas (CTCL) are a group of skin neoplasms that originate from T lymphocytes and are difficult to treat in advanced stages. The present study is aimed at the identification of tumor-specific antigens from a human testis cDNA library using human sera known as the SEREX (serological identification of recombinantly expressed genes) approach. A cDNA library from normal testicle tissue was prepared and approximately 2 million recombinants were screened with sera from Sé zary Syndrome and Mycosis fungoides patients. A total of 28 positive clones belonging to 15 different genes͞ORFs were identified, including five hitherto unknown sequences. Whereas control sera did not react with most clones, 11-71% sera from CTCL patients were reactive against the identified clones. Expression analysis on 28 normal control and 17 CTCL tissues by reverse transcription-PCR (RT-PCR) and Northern blotting revealed seven ubiquitously distributed antigens, six differentially expressed antigens (several normal tissues were positive), and two tumor-specific antigens that were expressed only in testis and tumor tissues: (i) A SCP-1-like sequence, which has already been detected in various tumors, has been found in one CTCL tumor and four sera of CTCL patients reacted with various SCP-1-like clones and (ii) a new sequence named cTAGE-1 (CTCLassociated antigen 1) was detected in 35% of CTCL tumor tissues and sera of 6͞18 patients reacted with this clone. The present study unravels CTCL-associated antigens independent of the T-cell receptor. The SCP-1-like gene and cTAGE-1 were shown to be immunogenic and immunologically tumor-specific and may therefore be candidates for immunotherapy targeting CTCL. mycosis fungoides ͉ Sé zary Syndrome ͉ SEREX ͉ cancer-testis-antigen ͉ tumor immunology

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“…Identification of tumor antigens and their optimal antigenic peptides over the past decade opened new approaches to the understanding of melanoma antigenicity and allowed development of peptide-based vaccine strategies. 1 The results of most clinical trials, however, indicated that progress must be made before peptide-based vaccines can be added to the therapeutic arsenal against melanoma. [2][3][4] Many studies demonstrated that immunization with antigenic peptides alone is not sufficient to elicit an efficient cytotoxic T lymphocyte (CTL) response, or even any response at all.…”

Section: Abstract: Melanoma; Cancer; Vaccine; Lipopeptides; Cd8 ϩ T mentioning

confidence: 99%

Lipopeptide‐based melanoma cancer vaccine induced a strong MART‐27‐35‐cytotoxic T lymphocyte response in a preclinal study

Gal

Prévost-Blondel

Lengagne

et al. 2001

Intl Journal of Cancer

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Key words: melanoma; cancer; vaccine; lipopeptides; CD8 ϩ T cell responses; peptides; immunotherapyCytotoxic T lymphocytes play a central role in the anti-tumor immune response by recognizing small antigenic peptides bound to major histocompatibility complex (MHC) class-I molecules on cancer cells. Identification of tumor antigens and their optimal antigenic peptides over the past decade opened new approaches to the understanding of melanoma antigenicity and allowed development of peptide-based vaccine strategies. 1 The results of most clinical trials, however, indicated that progress must be made before peptide-based vaccines can be added to the therapeutic arsenal against melanoma. [2][3][4] Many studies demonstrated that immunization with antigenic peptides alone is not sufficient to elicit an efficient cytotoxic T lymphocyte (CTL) response, or even any response at all. Formulation of the antigenic peptide is critical in vaccine development, because it conditions the vaccine capacity to induce effective and long-lasting anti-tumor immunity. Inappropriate modes of peptide delivery can even lead to antigen-specific tolerance instead of protection. 5 Lack of costimulation or T cell help activity has been proposed as a possible explanation for this phenomenon. Thus, to elicit specific CTL responses, peptide vaccine strategies must take into account additional factors, such as vectors, adjuvants and CD4 ϩ T cell help, all of which probably provide essential secondary signals. In this respect, professional antigen-presenting cells (APCs) are tools of choice in anti-tumor vaccine strategies. Encouraging results were obtained in a recent anti-melanoma vaccine trial using dendritic cells pulsed with tumor-associated antigenic peptides and a helper peptide. 6 Nevertheless, the procedure involved (in vitro generation, pulse and reinjection of these cells) was cumbersome and it increased the risk of bacterial contamination. Thus, we chose to develop a formulation that brings the benefits of synthetic peptides, assures T cell help via a strong CD4 epitope and might allow uptake by dendritic cells at the injection site.Lipopeptide formulations have been successfully used to induce anti-viral CTL responses in mice, 7-9 in monkeys 10 and in human clinical trials. [11][12][13] The influence of helper T lymphocytes (HTLs) stimulated by CD4 epitopes in inducing strong and long-lasting antigen-specific CTL responses in vivo 11,14 -16 and in vitro 17 has also been demonstrated. Therefore, to induce a strong melanoma specific CTL response, we included a CD4 epitope in our lipopeptide construct, which resulted in a simple vaccine formulation. MART-1 was selected as melanoma target antigen because of its very frequent expression in melanoma 18 and its well-known immunogenicity. 19 Moreover, the immunodominant peptide of this antigen, MART 27-35, is restricted to HLA-A2, expressed in 45% of the Caucasian population, which makes it a good candidate for vaccination. The TT830-843 peptide, derived from tetanus toxoid, was chosen as a s...

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T‐cell recognition of melanoma‐associated antigens

Cited by 110 publications

References 56 publications

TCR reconstitution in Jurkat reporter cells facilitates the identification of novel tumor antigens by cDNA expression cloning

TCR reconstitution in Jurkat reporter cells facilitates the identification of novel tumor antigens by cDNA expression cloning

Serological detection of cutaneous T-cell lymphoma-associated antigens

Lipopeptide‐based melanoma cancer vaccine induced a strong MART‐27‐35‐cytotoxic T lymphocyte response in a preclinal study

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