PMID- 10389916
OWN - NLM
STAT- MEDLINE
DCOM- 19990930
LR  - 20210102
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 5
IP  - 6
DP  - 1999 Jun
TI  - A Phase I study of active immunotherapy with carcinoembryonic antigen peptide 
      (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with 
      metastatic malignancies expressing carcinoembryonic antigen.
PG  - 1331-8
AB  - Dendritic cells (DCs), antigen-presenting cells capable of priming naive T cells 
      to specific antigens in an HLA-restricted fashion, have been demonstrated to 
      induce protective T cell-mediated immunity in tumor-bearing animals. We performed 
      this study to test the safety, feasibility, and clinical response of 
      immunizations with in vitro-generated DCs, loaded with an HLA-A2-restricted 
      peptide fragment of the tumor antigen carcinoembryonic antigen (CEA), for the 
      treatment of patients with advanced CEA-expressing malignancies. Cell 
      preparations enriched for autologous DCs were generated from the patients' 
      plastic adherent peripheral blood mononuclear cells in serum-free media 
      supplemented with granulocyte macrophage colony-stimulating factor and 
      interleukin-4. Within the cell preparation, 66% of the cells expressed the 
      phenotype typical for DCs (CD86high, HLA-DRhigh, and CD14low). The DCs were 
      loaded with the CEA peptide CAP-1 and cryopreserved. Groups of three to six 
      patients received four weekly or biweekly i.v. infusions of the CAP-1-loaded DC 
      in escalating dose levels of 1 x 10(7), 3 x 10(7), and 1 x 10(8) cells/dose. A 
      subset of the patients in the last group also received intradermal injections of 
      1 x 10(6) DCs. There were no toxicities directly referable to the treatments. One 
      patient had a minor response, and one had stable disease. Skin punch biopsy at DC 
      injection sites demonstrated pleomorphic infiltrates in the three patients 
      evaluated. We conclude that it is feasible and safe to generate and administer 
      large numbers of previously cryopreserved DCs loaded with CAP-1 peptide to 
      patients with advanced malignancies.
FAU - Morse, M A
AU  - Morse MA
AD  - Department of Medicine, Duke University Medical Center, Durham, North Carolina 
      27710, USA. morse004@mc.duke.edu
FAU - Deng, Y
AU  - Deng Y
FAU - Coleman, D
AU  - Coleman D
FAU - Hull, S
AU  - Hull S
FAU - Kitrell-Fisher, E
AU  - Kitrell-Fisher E
FAU - Nair, S
AU  - Nair S
FAU - Schlom, J
AU  - Schlom J
FAU - Ryback, M E
AU  - Ryback ME
FAU - Lyerly, H K
AU  - Lyerly HK
LA  - eng
GR  - M01RR00030/RR/NCRR NIH HHS/United States
GR  - U01CA72162-01/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (Antigens, CD)
RN  - 0 (Carcinoembryonic Antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Peptide Fragments)
RN  - 9009-79-4 (Rheumatoid Factor)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Antinuclear/blood
MH  - Antigens, CD/metabolism
MH  - Carcinoembryonic Antigen/biosynthesis/blood/*immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology/metabolism/*transplantation
MH  - Female
MH  - HLA-A2 Antigen/immunology
MH  - Humans
MH  - Immunotherapy, Active/*methods
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/blood/immunology/mortality/*therapy
MH  - Peptide Fragments/*immunology
MH  - Rheumatoid Factor/blood
MH  - Survival Rate
MH  - Transplantation, Autologous/immunology
EDAT- 1999/07/02 00:00
MHDA- 1999/07/02 00:01
CRDT- 1999/07/02 00:00
PHST- 1999/07/02 00:00 [pubmed]
PHST- 1999/07/02 00:01 [medline]
PHST- 1999/07/02 00:00 [entrez]
PST - ppublish
SO  - Clin Cancer Res. 1999 Jun;5(6):1331-8.