PMID- 16061868
OWN - NLM
STAT- MEDLINE
DCOM- 20060105
LR  - 20230413
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 11
IP  - 15
DP  - 2005 Aug 1
TI  - Dendritic cell vaccination in glioblastoma patients induces systemic and 
      intracranial T-cell responses modulated by the local central nervous system tumor 
      microenvironment.
PG  - 5515-25
AB  - PURPOSE: We previously reported that autologous dendritic cells pulsed with 
      acid-eluted tumor peptides can stimulate T cell-mediated antitumor immune 
      responses against brain tumors in animal models. As a next step in vaccine 
      development, a phase I clinical trial was established to evaluate this strategy 
      for its feasibility, safety, and induction of systemic and intracranial T-cell 
      responses in patients with glioblastoma multiforme. EXPERIMENTAL DESIGN: Twelve 
      patients were enrolled into a multicohort dose-escalation study and treated with 
      1, 5, or 10 million autologous dendritic cells pulsed with constant amounts (100 
      mug per injection) of acid-eluted autologous tumor peptides. All patients had 
      histologically proven glioblastoma multiforme. Three biweekly intradermal 
      vaccinations were given; and patients were monitored for adverse events, 
      survival, and immune responses. The follow-up period for this trial was almost 5 
      years. RESULTS: Dendritic cell vaccinations were not associated with any evidence 
      of dose-limiting toxicity or serious adverse effects. One patient had an 
      objective clinical response documented by magnetic resonance imaging. Six 
      patients developed measurable systemic antitumor CTL responses. However, the 
      induction of systemic effector cells did not necessarily translate into objective 
      clinical responses or increased survival, particularly for patients with actively 
      progressing tumors and/or those with tumors expressing high levels of 
      transforming growth factor beta(2) (TGF-beta(2)). Increased intratumoral 
      infiltration by cytotoxic T cells was detected in four of eight patients who 
      underwent reoperation after vaccination. The magnitude of the T-cell infiltration 
      was inversely correlated with TGF-beta(2) expression within the tumors and 
      positively correlated with clinical survival (P = 0.047). CONCLUSIONS: Together, 
      our results suggest that the absence of bulky, actively progressing tumor, 
      coupled with low TGF-beta(2) expression, may identify a subgroup of glioma 
      patients to target as potential responders in future clinical investigations of 
      dendritic cell-based vaccines.
FAU - Liau, Linda M
AU  - Liau LM
AD  - Division of Neurosurgery, Department of Surgery, The Brain Research Institute, 
      David Geffen School of Medicine at University of California at Los Angeles, 
      University of California Los Angeles, Los Angeles, California 90095, USA. 
      lliau@mednet.ucla.edu
FAU - Prins, Robert M
AU  - Prins RM
FAU - Kiertscher, Sylvia M
AU  - Kiertscher SM
FAU - Odesa, Sylvia K
AU  - Odesa SK
FAU - Kremen, Thomas J
AU  - Kremen TJ
FAU - Giovannone, Adrian J
AU  - Giovannone AJ
FAU - Lin, Jia-Wei
AU  - Lin JW
FAU - Chute, Dennis J
AU  - Chute DJ
FAU - Mischel, Paul S
AU  - Mischel PS
FAU - Cloughesy, Timothy F
AU  - Cloughesy TF
FAU - Roth, Michael D
AU  - Roth MD
LA  - eng
GR  - CA82666/CA/NCI NIH HHS/United States
GR  - CA91545/CA/NCI NIH HHS/United States
GR  - M01-RR00865/RR/NCRR NIH HHS/United States
GR  - T32-CA009120/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
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 (Cancer Vaccines)
RN  - 0 (Peptides)
RN  - 0 (RNA, Messenger)
RN  - 0 (TGFB2 protein, human)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cancer Vaccines/*metabolism
MH  - Central Nervous System/*metabolism
MH  - Central Nervous System Neoplasms/*pathology/*therapy
MH  - Cohort Studies
MH  - Dendritic Cells/*cytology/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - Peptides/chemistry
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes/*metabolism
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Time Factors
MH  - Transforming Growth Factor beta/metabolism
MH  - Transforming Growth Factor beta2
MH  - Treatment Outcome
EDAT- 2005/08/03 09:00
MHDA- 2006/01/06 09:00
CRDT- 2005/08/03 09:00
PHST- 2005/08/03 09:00 [pubmed]
PHST- 2006/01/06 09:00 [medline]
PHST- 2005/08/03 09:00 [entrez]
AID - 11/15/5515 [pii]
AID - 10.1158/1078-0432.CCR-05-0464 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2005 Aug 1;11(15):5515-25. doi: 10.1158/1078-0432.CCR-05-0464.