Dendritoma vaccination combined with low dose interleukin-2 in metastatic melanoma patients induced immunological and clinical responses

• Published in: International journal of oncology Vol. 28; no. 3; pp. 585 - 593
• Main Authors: Wei, Yanzhang, Sticca, Robert, Holmes, Lillia, Burgin, Kelly, Li, Jinhua, Williamson, Jane, Evans, Lyndon, Smith, Samuel, Stephenson, Joseph, Wagner, Thomas
• Format: Journal Article
• Language: English
• Published: Athens Editorial Academy of the International Journal of Oncology 01.03.2006
• Subjects: Adult; Aged; Biological and medical sciences; Cancer Vaccines - therapeutic use; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Dendritic Cells - cytology; Dendritic Cells - immunology; Dermatology; Female; Flow Cytometry; Humans; Hybrid Cells - immunology; Hybrid Cells - transplantation; Immunotherapy, Adoptive - methods; Interferon-gamma - metabolism; Interleukin-2 - therapeutic use; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - pathology; Male; Medical sciences; Melanoma - immunology; Melanoma - pathology; Melanoma - therapy; Middle Aged; Neoplasm Metastasis; Pilot Projects; Skin Neoplasms - immunology; Skin Neoplasms - pathology; Skin Neoplasms - therapy; Treatment Outcome; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Human; clinical study; Dendritic cell; Low dose; Vaccination; Cytokine; melanoma; Malignant tumor; Metastasis; Prevention; fusion; Cancerology; Treatment; Interleukin 2; Antigen presenting cell; Immunotherapy; tumor; Malignant melanoma; Advanced stage; dendritoma
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.28.3.585

A pilot clinical trial using dendritomas, purified hybrids from the fusion of dendritic/tumor cells combined with a low dose of IL-2, in metastatic melanoma patients was conducted in order to determine its safety and potential immunological and clinical responses. Ten metastatic melanoma patients were enrolled into this study. Dendritoma vaccines were created by fusing dendritic cells stained with green fluorescent dye with irradiated autologous tumor cells stained with red fluorescent dye and purifying the hybrids using immediate fluorescent-activated cell sorting. Initial vaccine was given subcutaneously and followed by IL-2 in serially elevated doses from 3-9 million units/m2 for 5 days. Repeated vaccinations were administered without IL-2, at 3-month intervals for a maximum of 5 times. Immune reactions were measured by the increase of interferon-gamma (IFN-gamma) expressing T cells. Vaccine doses ranged from 250,000 to 1,000,000 dendritomas. There was no grade 2 or higher toxicity directly attributable to the vaccine. All patients experienced toxicity due to IL-2 administration (9-grade 2, 3-grade 3, 1-grade 4). Eight of nine evaluable patients demonstrated immunologic reactions by increased IFN-gamma expressing T cells. One patient developed partial response at 12 weeks after the first vaccine. Nine months later, this patient achieved a complete response. In addition, two patients had stable disease for 9 and 4 months, respectively; one patient had a mixed response. Our findings demonstrated that dendritoma vaccines with a low dose of IL-2 can be safely administered to patients with metastatic melanoma and induce immunological and clinical responses.