PMID- 9500607
OWN - NLM
STAT- MEDLINE
DCOM- 19980402
LR  - 20220225
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 4
IP  - 3
DP  - 1998 Mar
TI  - Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic 
      cells.
PG  - 328-32
AB  - 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.
FAU - Nestle, F O
AU  - Nestle FO
AD  - Department of Dermatology, University of Zurich Medical School, Switzerland.
FAU - Alijagic, S
AU  - Alijagic S
FAU - Gilliet, M
AU  - Gilliet M
FAU - Sun, Y
AU  - Sun Y
FAU - Grabbe, S
AU  - Grabbe S
FAU - Dummer, R
AU  - Dummer R
FAU - Burg, G
AU  - Burg G
FAU - Schadendorf, D
AU  - Schadendorf D
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Peptides)
SB  - IM
CIN - Nat Med. 1998 Mar;4(3):269-70. PMID: 9500593
MH  - Adult
MH  - Aged
MH  - Antigens, Neoplasm/therapeutic use
MH  - Cancer Vaccines/*therapeutic use
MH  - *Dendritic Cells
MH  - Female
MH  - Humans
MH  - Hypersensitivity, Delayed
MH  - Lung Neoplasms/secondary
MH  - Male
MH  - Melanoma/*therapy
MH  - Middle Aged
MH  - Peptides/therapeutic use
MH  - Skin Tests
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Tomography
MH  - *Vaccination
EDAT- 1998/03/21 00:00
MHDA- 1998/03/21 00:01
CRDT- 1998/03/21 00:00
PHST- 1998/03/21 00:00 [pubmed]
PHST- 1998/03/21 00:01 [medline]
PHST- 1998/03/21 00:00 [entrez]
AID - 10.1038/nm0398-328 [doi]
PST - ppublish
SO  - Nat Med. 1998 Mar;4(3):328-32. doi: 10.1038/nm0398-328.