Fusion Cell Vaccination of Patients with Metastatic Breast and Renal Cancer Induces Immunological and Clinical Responses

• Published in: Clinical cancer research Vol. 10; no. 14; pp. 4699 - 4708
• Main Authors: AVIGAN, David, VASIR, Baldev, GIALLAMBARDO, Nancy, STONE, Carolyn, SCHADT, Kim, DOLGOFF, Jennifer, TETREAULT, Jean-Claude, VILLARROEL, Marisa, KUFE, Donald, JIANLIN GONG, BORGES, Virginia, ZEKUI WU, UHL, Lynne, ATKINS, Michael, MIER, James, MCDERMOTT, David, SMITH, Therese
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.07.2004
• Subjects: Antineoplastic agents; Biological and medical sciences; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cell Proliferation - drug effects; Cell Separation; Coculture Techniques; Dendritic Cells - cytology; Dendritic Cells - immunology; Female; Flow Cytometry; Hemocyanins - immunology; Hemocyanins - pharmacology; Humans; Hybrid Cells - cytology; Hybrid Cells - immunology; Immunohistochemistry; Interferon-gamma - biosynthesis; Kidney Neoplasms - immunology; Kidney Neoplasms - pathology; Kidney Neoplasms - therapy; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Treatment Outcome; Tumor Cells, Cultured; Tumors; Vaccination - methods; Kidney disease; Human; Urinary system disease; Vaccination; Breast cancer; Metastasis; Malignant tumor; Cell fusion; Prevention; Mammary gland diseases; Kidney cancer; Advanced stage; Mammary gland
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-0347

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 × 10 5 to 4 × 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-γ 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.