Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA.
We have developed an individualized melanoma vaccine based on transfection of autologous dendritic cells (DCs) with autologous tumor-mRNA. Dendritic cells loaded with complete tumor-mRNA may generate an immune response against a broad repertoire of antigens, including unique patient-specific antigens. The purpose of the present phase I/II trial was to evaluate the feasibility and safety of the vaccine, and the ability of the DCs to elicit T-cell responses in melanoma patients. Further, we compared intradermal (i.d.) and intranodal (i.n.) vaccine administration. Twenty-two patients with advanced malignant melanoma were included, each receiving four weekly vaccines. Monocyte-derived DCs were transfected with tumor-mRNA by electroporation, matured and cryopreserved. We obtained successful vaccine production for all patients elected. No serious adverse effects were observed. A vaccine-specific immune response was demonstrated in 9/19 patients evaluable by T-cell assays (T-cell proliferation/interferon-gamma ELISPOT) and in 8/18 patients evaluable by delayed-type hypersensitivity (DTH) reaction. The response was demonstrated in 7/10 patients vaccinated intradermally and in 3/12 patients vaccinated intranodally. We conclude that immuno-gene-therapy with the described DC-vaccine is feasible and safe, and that the vaccine can elicit in vivo T-cell responses against antigens encoded by the transfected tumor-mRNA. The response rates do not suggest an advantage in applying i.n. vaccination.
Kyte
J A
JA
Section for Immunotherapy, Department of Immunology, Cancer Research Institute, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway. j.a.kyte@klinmed.uio.no
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Aamdal
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Kvalheim
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Dueland
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Hauser
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Gullestad
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Ryder
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Lislerud
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Hammerstad
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Gaudernack
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D000328:Adult; D000368:Aged; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D017690:Cell Transplantation; D003713:Dendritic Cells; D004285:Dogs; D018274:Electroporation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D019496:Cancer Vaccines; D012333:RNA, Messenger