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

Abstract

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/m 2 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-Á (IFN-Á) 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-Á 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.

Generation of highly pure fusions of colorectal carcinoma and antigen-presenting cells

“…Compared to other methods, there is no need for tumor-specific peptide isolation, processing, and characterization [15]. Moreover, it is known that the antigen-presenting machinery of an APC works more effectively and efficiently when the antigen is synthesized inside rather than outside the cell [16].…”

In situ Expression of Tumor Antigens by Messenger RNA–Electroporated Dendritic Cells in Lymph Nodes of Melanoma Patients

“…These include viral vectors (8), RNA encoding tumor antigen (9)(10)(11)(12)(13)(14), whole tumor cell contents (apoptotic tumor cells or tumor cell lysate; refs. [15][16][17], and fusion of tumor cells with DC (18,19). The use of DNA or RNA encoding tumor antigens, whole tumor RNA, or tumor lysates to load DC is attractive because no knowledge of nominal epitopes in the tumor antigen is required, nor is there a restriction for the HLA type of the patient.…”

Novel dendritic cell-based vaccination in late stage melanoma

“…The average survival of 9 of the 10 patients was 198 days with 1 patient alive and disease-free 12 years after initial vaccination. 64 The phase IIa trial vaccinated 15 patients with stage IV melanoma. Each patient received a vaccination every 6 weeks at a dose ranging from 250 000-1 000 000 or more dendritomas up to 6 times depending on the availability of dendritomas and tumor cells.…”