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Cited by 2,862Immunotherapy and Immune ResponsesCutaneous Melanoma Detection and ManagementCancer Immunotherapy and Biomarkers

Vaccination of melanoma patients with peptide- or tumorlysate-pulsed dendritic cells

Nestle, Frank O., Alijagic, Selma, Gilliet, Michel, Sun, Yuansheng, Grabbe, Stephan, Dummer, Reinhard, Burg, Günter, Schadendorf, Dirk·1998·Nature Medicine
DOI 10.1038/nm0398-328
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Abstract

Melanoma is the main cause of death in patients with skin cancer. Cytotoxic T lymphocytes (CTLs) attack melanoma cells in an HLA-restricted and tumor antigen-specific manner. Several melanoma-associated tumor antigens have been identified. 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 response. Mouse studies have demonstrated the potent capacity of DCs to induce antitumor immunity. 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 delayed-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.

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  • Both the T cell pools of healthy individuals and cancer patients contain T cells that can identify KRAS mutation; after vaccination those T cells can be selectively expanded in tumor patients.

    “Both the T cell pools of healthy individuals and cancer patients contain T cells that can identify KRAS mutation. After vaccination those T cells can be selectively expanded in tumor patients.”

    From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [86]

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Authors
Nestle, F. O., Alijagic, S., Gilliet, M., Sun, Y., Grabbe, S., Dummer, R., Burg, G., & Schadendorf, D.
Affiliations
  • University of Zurich (CH)
  • German Cancer Research Center (DE)
  • University of Münster (DE)
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
1998-03
Volume
4
Issue
3
Pages
328-332
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm0398-328
OpenAlex
W2066964346
Cited by
2,862
References
26
Citations by year
2026: 14 · 2025: 9 · 2024: 8 · 2023: 18 · 2022: 18 · 2021: 21 · 2020: 58 · 2019: 40 · 2018: 36 · 2017: 31 · 2016: 43 · 2015: 32 · 2014: 52 · 2013: 55 · 2012: 57
FWCI
94.68
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
melanoma, dendritic cell vaccination, peptide-pulsed dendritic cells, tumor lysate, autologous dendritic cells, cytotoxic T lymphocytes, keyhole limpet hemocyanin, delayed-type hypersensitivity, metastatic melanoma, tumor antigens, antitumor immunity, vaccine safety
MeSH terms
Adult, Aged, Antigens, Neoplasm, Dendritic Cells, Female, Humans, Hypersensitivity, Delayed, Lung Neoplasms, Male, Melanoma, Middle Aged, Peptides, Skin Tests, T-Lymphocytes, Cytotoxic, Tomography, Vaccination, Cancer Vaccines

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