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Immuno-gene therapy of cancer with tumour-mRNA transfected dendritic cells

Kyte, Jon A ; Gaudernack, Gustav

Cancer Immunology, Immunotherapy, 2006-11, Vol.55 (11), p.1432-1442 [Periódico revisado por pares]

Germany: Springer Nature B.V

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Título:
Immuno-gene therapy of cancer with tumour-mRNA transfected dendritic cells
Autor: Kyte, Jon A ; Gaudernack, Gustav
Assuntos: Antigens ; Cancer therapies ; Cancer Vaccines - chemistry ; Clinical Trials as Topic ; Dendritic cells ; Dendritic Cells - cytology ; Dendritic Cells - immunology ; Gene therapy ; Genetic Therapy - methods ; Humans ; Immune system ; Immunotherapy ; Immunotherapy - methods ; Lymphocytes ; Male ; Melanoma ; Neoplasms - immunology ; Neoplasms - metabolism ; Patients ; Prostate cancer ; Prostatic Neoplasms - therapy ; RNA, Messenger - metabolism ; Skin cancer ; Symposium Paper ; T-Lymphocytes - metabolism ; Transfection ; Vaccines
É parte de: Cancer Immunology, Immunotherapy, 2006-11, Vol.55 (11), p.1432-1442
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-3
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ObjectType-Review-1
Descrição: We have developed immuno-gene therapy for malignant melanoma and prostate cancer. The therapy is based on monocyte-derived dendritic cells (DCs) that are transfected with autologous melanoma-mRNA or mRNA from three prostate cancer cell lines (DU-145, LN-CaP and PC-3). A broad spectrum of tumour-associated antigens will be included in both DC-vaccines. The use of autologous melanoma-mRNA moreover allows targeting of individual tumour antigens that are specific to each patient. Effective protocols have been established for mRNA-transfection by square wave electroporation and for the generation of clinical grade DCs. A full scale preclinical evaluation demonstrated in vitro T cell responses in 6/6 advanced melanoma patients. The responses were specific to antigens encoded by the transfected tumour-mRNA. Recently, we have conducted two phase I/II trials, in advanced malignant melanoma and androgen-resistant prostate cancer. Successful vaccine preparations were obtained for all 41 patients elected. No serious adverse effects were observed. Specific T cell responses (T cell proliferation and/or IFNgamma ELISPOT) were demonstrated in 9/19 evaluable melanoma patients and in 12/19 prostate cancer patients. The response rates were higher for patients receiving intradermal vaccination, compared to intranodal injection. Thirteen prostate cancer patients developed a decrease in log-slope PSA. The PSA-response was significantly related to the T cell response (P=0.002). We conclude that the DC-vaccine is feasible and safe, and that T cell responses are elicited in about 50% of patients.
Editor: Germany: Springer Nature B.V
Idioma: Inglês

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Immuno-gene therapy of cancer with tumour-mRNA transfected dendritic cells

Kyte, Jon A ; Gaudernack, Gustav

Germany: Springer Nature B.V

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