PMID- 11135227
OWN - NLM
STAT- MEDLINE
DCOM- 20010208
LR  - 20201212
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 89
IP  - 12
DP  - 2000 Dec 15
TI  - Intratumoral injection of dendritic cells derived in vitro in patients with 
      metastatic cancer.
PG  - 2646-54
AB  - BACKGROUND: Dendritic cells (DCs) are potent initiators of immune responses, and 
      the infiltration of DCs into tumors may confer an improved prognosis. Whether the 
      injection of DCs directly into tumors can mediate biologic activity was examined. 
      METHODS: Patients with metastatic dermal or subcutaneous tumors received 
      granulocyte-macrophage-colony stimulating factor to increase the numbers of 
      peripheral blood monocyte precursors. DCs were then generated from monocytes 
      obtained by phlebotomy with granulocyte-macrophage-colony stimulating factor and 
      interleukin-4 in autologous plasma. Tumors were injected at multiple sites with 
      30 million autologous DCs per tumor. RESULTS: Seven patients with melanoma and 
      three patients with breast carcinoma were treated. Injections were well 
      tolerated. Regression of the injected tumors, beginning as early as 4 days after 
      injection, was observed in four patients with melanoma and in two patients with 
      breast carcinoma. Biopsies of regressing lesions showed lymphocyte infiltration 
      associated with DCs and necrosis. Neutrophils and macrophages were not evident. 
      Lymphocytes expanded from the regressing tumors proliferated in response to heat 
      shock proteins, HSP70 and gp96, derived from autologous tumor. The DCs injected 
      produced interferon-alpha and expressed Fas ligand mRNA but did not exhibit 
      cytolytic activity in vitro. Expression of the costimulatory molecule, B7-2 
      (CD86), decreased on DCs after intratumoral injection. CONCLUSIONS: This pilot 
      study demonstrates that DCs derived in vitro can exist viably after intratumoral 
      injection and can mediate biologic activity in situ. Tumor-derived heat shock 
      proteins may be involved in the antitumor activity observed.
CI  - Copyright 2000 American Cancer Society.
FAU - Triozzi, P L
AU  - Triozzi PL
AD  - The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute/The 
      Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA. 
      pierre.triozzi@ccc.uab.edu
FAU - Khurram, R
AU  - Khurram R
FAU - Aldrich, W A
AU  - Aldrich WA
FAU - Walker, M J
AU  - Walker MJ
FAU - Kim, J A
AU  - Kim JA
FAU - Jaynes, S
AU  - Jaynes S
LA  - eng
GR  - P30CA16058/CA/NCI NIH HHS/United States
GR  - R01 CA67830-01/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Controlled Clinical Trial
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  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Antigens, CD)
RN  - 0 (B7-2 Antigen)
RN  - 0 (CD86 protein, human)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Integrin alphaXbeta2)
RN  - 0 (Membrane Glycoproteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antigens, CD/analysis
MH  - B7-2 Antigen
MH  - Cell Transplantation
MH  - Dendritic Cells/*immunology/transplantation
MH  - Female
MH  - Flow Cytometry
MH  - HLA-DR Antigens/analysis
MH  - Heat-Shock Proteins/analysis
MH  - Humans
MH  - Immunohistochemistry
MH  - *Immunotherapy, Adoptive
MH  - Injections, Intralesional
MH  - Integrin alphaXbeta2/analysis
MH  - Male
MH  - Membrane Glycoproteins/analysis
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neoplasms/immunology/pathology/*therapy
MH  - Pilot Projects
MH  - Treatment Outcome
EDAT- 2001/01/03 11:00
MHDA- 2001/03/03 10:01
CRDT- 2001/01/03 11:00
PHST- 2001/01/03 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2001/01/03 11:00 [entrez]
AID - 10.1002/1097-0142(20001215)89:12<2646::AID-CNCR18>3.0.CO;2-A [pii]
AID - 10.1002/1097-0142(20001215)89:12<2646::aid-cncr18>3.0.co;2-a [doi]
PST - ppublish
SO  - Cancer. 2000 Dec 15;89(12):2646-54. doi: 
      10.1002/1097-0142(20001215)89:12<2646::aid-cncr18>3.0.co;2-a.