Cancer Immunology, Immunotherapy

, Volume 55, Issue 11, pp 1432–1442

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

Symposium Paper

DOI: 10.1007/s00262-006-0161-7

Cite this article as:
Kyte, J.A. & Gaudernack, G. Cancer Immunol Immunother (2006) 55: 1432. doi:10.1007/s00262-006-0161-7

Abstract

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 IFNγ 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.

Keywords

Immuno-gene therapyDendritic cellsRNA transfectionMelanomaProstate cancerClinical trial

Abbreviations

DC

Dendritic cell

PBMC

Peripheral blood mononuclear cell

EGFP

Enhanced green fluorescent protein

hTERT

Human telomerase reverse transcriptase

TRAP

Telomeric repeat amplification protocol

EBV-cells

Epstein Barr virus-transformed cell-lines

PSA

Prostate specific antigen

TLR

Toll-like receptor

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Section for Immunotherapy, Department of Immunology, Cancer Research Institute, The Norwegian Radium HospitalUniversity of OsloOsloNorway