Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses.
OBJECTIVE
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.


METHODS
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.
Avigan
David
D
Beth Israel Deaconess Medical Center and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Vasir
Baldev
B
Gong
Jianlin
J
Borges
Virginia
V
Wu
Zekui
Z
Uhl
Lynne
L
Atkins
Michael
M
Mier
James
J
McDermott
David
D
Smith
Therese
T
Giallambardo
Nancy
N
Stone
Carolyn
C
Schadt
Kim
K
Dolgoff
Jennifer
J
Tetreault
Jean-Claude
JC
Villarroel
Marisa
M
Kufe
Donald
D
D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006433:Hemocyanins / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology / Q000276:immunology; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014611:Vaccination / Q000379:methods
D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin