PMID- 15269142
OWN - NLM
STAT- MEDLINE
DCOM- 20050119
LR  - 20201212
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 10
IP  - 14
DP  - 2004 Jul 15
TI  - Fusion cell vaccination of patients with metastatic breast and renal cancer 
      induces immunological and clinical responses.
PG  - 4699-708
AB  - PURPOSE: Dendritic cells (DCs) are potent antigen-presenting cells that are 
      uniquely capable of inducing tumor-specific immune responses. We have conducted a 
      Phase I trial in which patients with metastatic breast and renal cancer were 
      treated with a vaccine prepared by fusing autologous tumor and DCs. EXPERIMENTAL 
      DESIGN: Accessible tumor tissue was disrupted into single cell suspensions. 
      Autologous DCs were prepared from adherent peripheral blood mononuclear cells 
      that were obtained by leukapheresis and cultured in granulocyte macrophage 
      colony-stimulating factor, interleukin 4, and autologous plasma. Tumor cells and 
      DCs were cocultured in the presence of polyethylene glycol to generate the 
      fusions. Fusion cells were quantified by determining the percentage of cells that 
      coexpress tumor and DC markers. Patients were vaccinated with fusion cells at 
      3-week intervals and assessed weekly for toxicity, and tumor response was 
      assessed at 1, 3, and 6 months after completion of vaccination. RESULTS: The 
      vaccine was generated for 32 patients. Twenty-three patients were vaccinated with 
      1 x 10(5) to 4 x 10(6) fusion cells. Fusion cells coexpressed tumor and DC 
      antigens and stimulated allogeneic T-cell proliferation. There was no significant 
      treatment-related toxicity and no clinical evidence of autoimmunity. In a subset 
      of patients, vaccination resulted in an increased percentage of CD4 and CD8+ T 
      cells expressing intracellular IFN-gamma in response to in vitro exposure to 
      tumor lysate. Two patients with breast cancer exhibited disease regressions, 
      including a near complete response of a large chest wall mass. Five patients with 
      renal carcinoma and one patient with breast cancer had disease stabilization. 
      CONCLUSIONS: Our findings demonstrate that fusion cell vaccination of patients 
      with metastatic breast and renal cancer is a feasible, nontoxic approach 
      associated with the induction of immunological and clinical antitumor responses.
FAU - Avigan, David
AU  - Avigan D
AD  - Beth Israel Deaconess Medical Center and Dana-Farber Cancer Institute, Harvard 
      Medical School, Boston, Massachusetts 02115, USA.
FAU - Vasir, Baldev
AU  - Vasir B
FAU - Gong, Jianlin
AU  - Gong J
FAU - Borges, Virginia
AU  - Borges V
FAU - Wu, Zekui
AU  - Wu Z
FAU - Uhl, Lynne
AU  - Uhl L
FAU - Atkins, Michael
AU  - Atkins M
FAU - Mier, James
AU  - Mier J
FAU - McDermott, David
AU  - McDermott D
FAU - Smith, Therese
AU  - Smith T
FAU - Giallambardo, Nancy
AU  - Giallambardo N
FAU - Stone, Carolyn
AU  - Stone C
FAU - Schadt, Kim
AU  - Schadt K
FAU - Dolgoff, Jennifer
AU  - Dolgoff J
FAU - Tetreault, Jean-Claude
AU  - Tetreault JC
FAU - Villarroel, Marisa
AU  - Villarroel M
FAU - Kufe, Donald
AU  - Kufe D
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9013-72-3 (Hemocyanins)
RN  - FV4Y0JO2CX (keyhole-limpet hemocyanin)
SB  - IM
MH  - Breast Neoplasms/*immunology/pathology/therapy
MH  - Cell Proliferation/drug effects
MH  - Cell Separation
MH  - Coculture Techniques
MH  - Dendritic Cells/cytology/immunology
MH  - Female
MH  - Flow Cytometry
MH  - Hemocyanins/immunology/pharmacology
MH  - Humans
MH  - Hybrid Cells/cytology/immunology
MH  - Immunohistochemistry
MH  - Interferon-gamma/biosynthesis
MH  - Kidney Neoplasms/*immunology/pathology/therapy
MH  - Male
MH  - Middle Aged
MH  - T-Lymphocytes/cytology/immunology/metabolism
MH  - Treatment Outcome
MH  - Tumor Cells, Cultured
MH  - Vaccination/methods
EDAT- 2004/07/23 05:00
MHDA- 2005/01/20 09:00
CRDT- 2004/07/23 05:00
PHST- 2004/07/23 05:00 [pubmed]
PHST- 2005/01/20 09:00 [medline]
PHST- 2004/07/23 05:00 [entrez]
AID - 10/14/4699 [pii]
AID - 10.1158/1078-0432.CCR-04-0347 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2004 Jul 15;10(14):4699-708. doi: 10.1158/1078-0432.CCR-04-0347.