Lack of tumor recognition by hTERT peptide 540-548-specific CD8+ T cells from melanoma patients reveals inefficient antigen processing

Ayyoub, Maha; Migliaccio, Marianna; Guillaume, Philippe; Líénard, Danielle; Cerottini, Jean‐Charles; Romero, Pedro; Lévy, Frédéric; Speiser, Daniel E.; Valmori, Danila

doi:10.1002/1521-4141(200109)31:9<2642::aid-immu2642>3.0.co;2-6

Cited by 74 publications

(53 citation statements)

References 27 publications

(43 reference statements)

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“…5 Effective therapeutic vaccination has been limited by many factors, including absence or low frequency and low avidity of antigen-specific T-cell precursors directed against self-antigens as a result of thymic negative selection, 6, 7 and various peripheral inhibitory mechanisms. 7,8,9,10 Tumor outgrowth is clearly not prevented even when large numbers of specific T cells are generated in high-risk cancer patients without clinical or radiological evidence of disease at the initiation of immunization. 11 At the same time, it has become evident that the use of immunotherapy based on adoptive cell transfer (ACT) can overcome many of the hurdles that hinder current vaccine-based approaches.…”

Section: Introductionmentioning

confidence: 99%

Increased intensity lymphodepletion and adoptive immunotherapy—how far can we go?

et al. 2006

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SummaryIn a recent clinical trial involving patients with metastatic melanoma, immunosuppressive conditioning with fludarabine and cyclophosphamide resulted in a 50% response rate and a robust long-term persistence of adoptively transferred T cells. Experimental findings indicate that lymphodepletion prior to adoptive transfer of tumor-specific T lymphocytes plays a key role in enhancing treatment efficacy by eliminating regulatory T cells and competing elements of the immune system ('cytokine sinks'). Newly emerging animal data suggest that more profound lymphoablative conditioning with autologous hematopoetic stem-cell rescue might further enhance treatment results. Here we review recent advances in adoptive immunotherapy of solid tumors and discuss the rationale for lymphodepleting conditioning. We also address safety issues associated with translating experimental animal results of total lymphoid ablation into clinical practice. Review criteriaThe PubMed and MEDLINE databases were searched for articles published until April 2006. Electronic early-release publications were also included. Only articles published in English were considered. The search terms used included "adoptive cell transfer", "lymphodepletion", "lymphopenia", "TBI", "homeostatic proliferation", "allogeneic transplant", "syngeneic transplant", "IPS" and "treatment related mortality". Full articles were obtained and references were checked for additional material when appropriate. References were chosen based on the best clinical or laboratory evidence, especially if data had been corroborated by published work from other centers. Priority was given to studies in high-impact-factor journals when available.

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Section: Introductionmentioning

confidence: 99%

Increased intensity lymphodepletion and adoptive immunotherapy—how far can we go?

et al. 2006

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“…TERTspecific CD8 þ T cells induced by peptide stimulation have failed to recognize TERT-expressing tumor cells owing to inefficient antigen stimulation. 12 These reports suggest that TERT-specific immune response can be activated in vitro and in vivo. However, TERT-specific immune responses against tumor cells in vivo are inefficient, likely due to host immune tolerance to TERT protein.…”

Section: Tert Expression In Tumorsmentioning

confidence: 99%

“…8,9 TERT-specific CD4 þ or CD8 þ T cells have been induced in vitro from healthy donors or cancer patients. [10][11][12][13][14][15][16][17][18] However, effective anti-TERT-specific tumor immunity is difficult to induce in vivo consistently. 11,17 It is thought that the low immunopotency of various vaccine formulas is due, in part, to poor antigen presentation by antigen-presenting cells (APCs) and/or tumor cells, weak TAA immunogenicity, limited activation of effector cells by APCs and/or immune tolerance to TAAs.…”

Section: Introductionmentioning

confidence: 99%

Immunity against breast cancer by TERT DNA vaccine primed with chemokine CCL21

et al. 2007

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Human telomerase reverse transcriptase (TERT) has been considered a potential tumor-associated antigen for active-specific immunotherapy. However, effective specific tumor antigen-specific immunity has been difficult to induce consistently by various TERT vaccine formulations. New adjuvant strategies have been employed, such as utilizing chemokines to attract T cells and antigen-presenting cells. Chemokine adjuvant strategies may enhance tumor antigen-specific immunity induced by vaccines. Therefore, we utilized chemokine ligand 21 (CCL21) as an adjuvant with a xenogeneic TERT DNA vaccine to induce tumor antigenspecific immunity against TERT-expressing breast cancer. The TERT DNA vaccine consisted of a plasmid containing the COOH terminal end of the TERT (cTERT) gene, encapsulated in multilayered liposomes with hemagglutinating virus of Japan coating. We demonstrated that CCL21 treatment before cTERT DNA vaccine, given intramuscularly, induced significantly higher anti-TERT specific cell-mediated immunity compared to cTERT DNA vaccine alone. Effective tumor antigen-specific immunity was shown both in prophylactic and therapeutic regimens against TS/A murine breast cancer. The study demonstrated that CCL21 administration before cTERT DNA vaccination significantly augmented tumor antigen-specific immunity against breast cancer.

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“…Specifically, CTL can be generated in vitro against a large panel of peptides that are not naturally produced and presented by tumour cells. 37,38 …”

Section: Tumour Antigensmentioning

confidence: 99%

“…Specifically, CTL can be generated in vitro against a large panel of peptides that are not naturally produced and presented by tumour cells. 37,38 Vaccination strategies Therapeutic vaccines for cancer aim at either enhancing or inducing protective TA-specific T-cell responses in vivo. Different strategies to achieve this are being explored, including vaccination with peptides, 22,31,39 -42 naked DNA encoding part of or whole TA, 43-47 recombinant virus, 48 -51 recombinant protein, 52,53 peptide coated dendritic cells (DCs) 54 -62 or peripheral blood mononuclear cells (PBMC) 63 and TA mRNA loaded DCs.…”

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confidence: 99%

Recent advances in tumour antigen‐specific therapy: In vivo veritas

Mahnke

Speiser

Luescher

et al. 2004

Intl Journal of Cancer

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Modern cancer therapies should strive not only to eliminate malignant tissues but also to preserve healthy tissues and the patient's quality of life. Antigen-specific immunotherapy approaches are promising for either aspect since they are designed to only act against tissues expressing 1 or more specified tumour antigens. In order to develop successful vaccine and adoptive transfer protocols, longitudinal monitoring of cancer patients taking part in clinical trials is mandatory. Here, in vivo expansion of antigenspecific cells, as well as their ex vivo functional status represent important parameters to be analysed. To obtain results that most closely reflect the cells' in vivo status, functional assays must be carried out with as little in vitro culturing as possible. The present minireview discusses recent advances in these domains. Key words: cancer vaccines; T cell monitoring; tetramers; immunotherapy Tumour antigensRapid advances in the identification of MHC class I-restricted tumour antigens (TA) and their antigenic peptides 1 took place at the end of the 20th century, engendering antigen (Ag)-specific immunotherapy approaches to cancer treatment. [2][3][4] In contrast, progress in the molecular identification of MHC class II restricted peptides of TA has been much slower. Although tumour-specific CD8 ϩ T-cell responses have been documented upon vaccination with MHC class I-restricted peptides, it could be shown in murine tumour models that the generation of potent and long-lasting anti-tumour immunity is improved when both MHC class I-and class II-restricted T-cell epitopes are included in tumour vaccines. [5][6][7] These observations fostered the search for TA-derived peptides that are presented by class II molecules in cancer patients and lead to the isolation of diverse CD4 ϩ T-cell clones specific for given TA, though the precise epitopes have not yet been identified in all cases. 8,9 The high number of human MHC class II alleles severely limits the applicability of many of the antigenic peptides identified thus far. An exception is the HLA-DP4 molecule. Indeed, 2 highly prevalent alleles encode its ␤ chain and their combined frequency reaches approximately 60% of the population world-wide. Two HLA-DP4-restricted tumour associated antigenic peptides have been identified thus far. 10,11 Moreover, detailed analysis of HLA-DP4 peptide binding may facilitate future searches of novel tumour antigenic peptides restricted by this frequently occurring class II MHC allele. 12 Another favourable trait is the "degenerate" DR binding of certain antigenic peptides, i.e., various TA-derived antigenic peptides have been reported to bind to diverse HLA-DR molecules. 13,14 The identification of TA-derived epitopes presented by MHC class II molecules is complicated by the lack of effective screening methods. Recently, by combination of a computer-based algorithm for MHC-binding with T-cell functional analyses, a class II-restricted epitope of carcinoembryonic Ag (CEA, aa 116 -140) was identified that is naturally proce...

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Lack of tumor recognition by hTERT peptide 540-548-specific CD8+ T cells from melanoma patients reveals inefficient antigen processing

Cited by 74 publications

References 27 publications

Increased intensity lymphodepletion and adoptive immunotherapy—how far can we go?

Increased intensity lymphodepletion and adoptive immunotherapy—how far can we go?

Immunity against breast cancer by TERT DNA vaccine primed with chemokine CCL21

Recent advances in tumour antigen‐specific therapy: In vivo veritas

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