Journal ArticleDOI
Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells.
Frank O. Nestle,Selma Alijagic,Michel Gilliet,Yuansheng Sun,Stephan Grabbe,Reinhard Dummer,Günter Burg,Dirk Schadendorf +7 more
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TLDR
Vaccination with autologous DCs generated from peripheral blood is a safe and promising approach in the treatment of metastatic melanoma and antigen-specific immunity was induced during DC vaccination.Abstract:
Melanoma is the main cause of death in patients with skin cancer1. Cytotoxic T lymphocytes (CTLs) attack melanoma cells in an HLA-restricted and tumor antigen-specific manner. Several melanoma-associated tumor antigens have been identified2. These antigens are suitable candidates for a vaccination therapy of melanoma. Dendritic cells (DCs) are antigen-presenting cells (APCs) specialized for the induction of a primary T-cell response3. Mouse studies have demonstrated the potent capacity of DCs to induce antitu-mor immunity4–11. In the present clinical pilot study, DCs were generated in the presence of granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin 4 (IL-4) and were pulsed with tumor lysate or a cocktail of peptides known to be recognized by CTLs, depending on the patient's HLA haplotype. Keyhole limpet hemocyanin (KLH) was added as a CD4 helper antigen and immunological tracer molecule. Sixteen patients with advanced melanoma were immunized on an outpatient basis. Vaccination was well tolerated. No physical sign of autoimmunity was detected in any of the patients. DC vaccination induced de-layed-type hypersensitivity (DTH) reactivity toward KLH in all patients, as well as a positive DTH reaction to peptide-pulsed DCs in 11 patients. Recruitment of peptide-specific CTLs to the DTH challenge site was also demonstrated. Therefore, antigen-specific immunity was induced during DC vaccination. Objective responses were evident in 5 out of 16 evaluated patients (two complete responses, three partial responses) with regression of metastases in various organs (skin, soft tissue, lung, pancreas) and one additional minor response. These data indicate that vaccination with autologous DCs generated from peripheral blood is a safe and promising approach in the treatment of metastatic melanoma. Further studies are necessary to demonstrate clinical effectiveness and impact on the survival of melanoma patients.read more
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Journal ArticleDOI
Immunobiology of Dendritic Cells
Jacques Banchereau,Francine Brière,Christophe Caux,Jean Davoust,Serge Lebecque,Yong-Jun Liu,Bali Pulendran,Karolina Palucka +7 more
TL;DR: Dendritic cells are antigen-presenting cells with a unique ability to induce primary immune responses and may be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell-mediated immune response.
Journal ArticleDOI
Cancer immunotherapy: moving beyond current vaccines.
TL;DR: Results in cancer vaccine trials are considered and alternate strategies that mediate cancer regression in preclinical and clinical models are highlighted.
Journal ArticleDOI
Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase
Catherine Uyttenhove,Luc Pilotte,Ivan Théate,Ivan Théate,Vincent Stroobant,Didier Colau,Nicolas Parmentier,Thierry Boon,Benoît Van den Eynde +8 more
TL;DR: It is shown that most human tumors constitutively express IDO, and that expression of IDO by immunogenic mouse tumor cells prevents their rejection by preimmunized mice, suggesting that the efficacy of therapeutic vaccination of cancer patients might be improved by concomitant administration of an IDO inhibitor.
Journal ArticleDOI
Taking dendritic cells into medicine
TL;DR: Some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy are presented.
Journal ArticleDOI
Antigen Presentation and T Cell Stimulation by Dendritic Cells
TL;DR: Dendritic cells take up antigens in peripheral tissues, process them into proteolytic peptides, and load these peptides onto major histocompatibility complex (MHC) class I and II molecules, thus initiating antigen-specific immune responses, or immunological tolerance.
References
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Journal ArticleDOI
Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha.
TL;DR: Cultured DCs are as efficient as antigen-specific B cells in presenting tetanus toxoid (TT) to specific T cell clones and their efficiency of antigen presentation can be further enhanced by specific antibodies via FcR- mediated antigen uptake.
Journal ArticleDOI
The dendritic cell system and its role in immunogenicity
TL;DR: Dendritic cells are specialized to mediate several physiologic components of immunogenicity such as the acquisition of antigens in tissues, the migration to lymphoid organs, and the identification and activation of antigen-specific T cells.
Journal ArticleDOI
Proliferating dendritic cell progenitors in human blood.
Nikolaus Romani,S Gruner,D. Brang,Eckhart Kämpgen,Angela Lenz,B Trockenbacher,G Konwalinka,Peter O. Fritsch,Ralph M. Steinman,Gerold Schuler +9 more
TL;DR: Large numbers of DC progenitors are observed in cord blood and in adult blood from healthy donors, which should facilitate future studies of their Fc epsilon RI and CD4 receptors, and their use in stimulating T cell-mediated resistance to viruses and tumors.
Journal ArticleDOI
Vaccination of patients with B–cell lymphoma using autologous antigen–pulsed dendritic cells
Frank J. Hsu,Claudia Benike,Francesco Fagnoni,Tina Marie Liles,Debra K. Czerwinski,Behnaz Taidi,Edgar G. Engleman,Ronald Levy +7 more
TL;DR: This pilot study investigated the ability of autologous dendritic cells pulsed ex vivo with tumor–specific idiotype protein to stimulate host antitumor immunity when infused as a vaccine in patients with follicular B–cell lymphoma.
Journal ArticleDOI
GM-CSF and TNF-α cooperate in the generation of dendritic Langerhans cells
TL;DR: It is demonstrated that cooperation between GM-CSF and tumour necrosis factor-α (TNF-α) is crucial for the generation of human dendritic/Langerhans cells from CD34+ haematopoietic progenitors.