PMID- 19789309
OWN - NLM
STAT- MEDLINE
DCOM- 20091222
LR  - 20211020
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 15
IP  - 19
DP  - 2009 Oct 1
TI  - Dendritic cell vaccination combined with CTLA4 blockade in patients with 
      metastatic melanoma.
PG  - 6267-76
LID - 10.1158/1078-0432.CCR-09-1254 [doi]
AB  - PURPOSE: Tumor antigen-loaded dendritic cells (DC) are believed to activate 
      antitumor immunity by stimulating T cells, and CTL-associated antigen 4 
      (CTLA4)-blocking antibodies should release a key negative regulatory pathway on T 
      cells. The combination was tested in a phase I clinical trial in patients with 
      advanced melanoma. EXPERIMENTAL DESIGN: Autologous DC were pulsed with 
      MART-1(26-35) peptide and administered with a dose escalation of the 
      CTLA4-blocking antibody tremelimumab. Sixteen patients were accrued to five dose 
      levels. Primary end points were safety and immune effects; clinical efficacy was 
      a secondary end point. RESULTS: Dose-limiting toxicities of grade 3 diarrhea and 
      grade 2 hypophysitis developed in two of three patients receiving tremelimumab at 
      10 mg/kg monthly. Four patients had an objective tumor response, two partial 
      responses and two complete responses, all melanoma free between 2 and 4 years 
      after study initiation. There was no difference in immune monitoring results 
      between patients with an objective tumor response and those without a response. 
      Exploratory gene expression analysis suggested that immune-related gene 
      signatures, in particular for B-cell function, may be important in predicting 
      response. CONCLUSION: The combination of MART-1 peptide-pulsed DC and 
      tremelimumab results in objective and durable tumor responses at the higher range 
      of the expected response rate with either agent alone.
FAU - Ribas, Antoni
AU  - Ribas A
AD  - Department of Medicine, Division of Hematology/Oncology, University of California 
      at Los Angeles, Los Angeles, California 90095-1782, USA. aribas@mednet.ucla.edu
FAU - Comin-Anduix, Begona
AU  - Comin-Anduix B
FAU - Chmielowski, Bartosz
AU  - Chmielowski B
FAU - Jalil, Jason
AU  - Jalil J
FAU - de la Rocha, Pilar
AU  - de la Rocha P
FAU - McCannel, Tara A
AU  - McCannel TA
FAU - Ochoa, Maria Teresa
AU  - Ochoa MT
FAU - Seja, Elizabeth
AU  - Seja E
FAU - Villanueva, Arturo
AU  - Villanueva A
FAU - Oseguera, Denise K
AU  - Oseguera DK
FAU - Straatsma, Bradley R
AU  - Straatsma BR
FAU - Cochran, Alistair J
AU  - Cochran AJ
FAU - Glaspy, John A
AU  - Glaspy JA
FAU - Hui, Liu
AU  - Hui L
FAU - Marincola, Francesco M
AU  - Marincola FM
FAU - Wang, Ena
AU  - Wang E
FAU - Economou, James S
AU  - Economou JS
FAU - Gomez-Navarro, Jesus
AU  - Gomez-Navarro J
LA  - eng
GR  - CA-16042/CA/NCI NIH HHS/United States
GR  - R01 CA129816/CA/NCI NIH HHS/United States
GR  - M01 RR000865/RR/NCRR NIH HHS/United States
GR  - P50 CA086306/CA/NCI NIH HHS/United States
GR  - P50 CA086306-100006/CA/NCI NIH HHS/United States
GR  - M01 RR000865-338786/RR/NCRR NIH HHS/United States
GR  - M01-RR-0865/RR/NCRR NIH HHS/United States
GR  - AI-28697/AI/NIAID NIH HHS/United States
GR  - U54 CA119347/CA/NCI NIH HHS/United States
GR  - P30 CA016042/CA/NCI NIH HHS/United States
GR  - P30 AI028697/AI/NIAID NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090929
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, Blocking)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Cancer Vaccines)
RN  - 0 (MART-1 Antigen)
RN  - 0 (MLANA protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Peptide Fragments)
RN  - QEN1X95CIX (tremelimumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Blocking/*administration & dosage/adverse effects
MH  - Antibodies, Monoclonal/administration & dosage/adverse effects
MH  - Antibodies, Monoclonal, Humanized
MH  - Antigens, CD/*immunology
MH  - Antigens, Neoplasm/administration & dosage/chemistry/metabolism
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage
MH  - CTLA-4 Antigen
MH  - Cancer Vaccines/*administration & dosage/adverse effects
MH  - Combined Modality Therapy
MH  - Dendritic Cells/immunology/metabolism/*transplantation
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Immunotherapy, Adoptive/*methods
MH  - K562 Cells
MH  - MART-1 Antigen
MH  - Male
MH  - Melanoma/pathology/*therapy
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neoplasm Proteins/administration & dosage/chemistry/metabolism
MH  - Peptide Fragments/administration & dosage/metabolism
PMC - PMC2765061
MID - NIHMS134485
COIS- Conflict of interest disclosure. Dr. Antoni Ribas has received commercial 
      research grants and honoraria from Pfizer Inc.; Dr. John A. Glaspy has received 
      speaker's bureau/honoraria from Pfizer Inc.; Dr. Jesus Gomez-Navarro is employed 
      by Pfizer Inc. The remaining authors have no conflicts of interest to report.
EDAT- 2009/10/01 06:00
MHDA- 2009/12/23 06:00
PMCR- 2010/10/01
CRDT- 2009/10/01 06:00
PHST- 2009/10/01 06:00 [entrez]
PHST- 2009/10/01 06:00 [pubmed]
PHST- 2009/12/23 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - 1078-0432.CCR-09-1254 [pii]
AID - 10.1158/1078-0432.CCR-09-1254 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2009 Oct 1;15(19):6267-76. doi: 10.1158/1078-0432.CCR-09-1254. 
      Epub 2009 Sep 29.