Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 2540
© 2005 American Society of Clinical Oncology

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Abstract

Phase I/II trial of vaccine therapy with tumor-RNA transfected dendritic cells in patients with advanced malignant melanoma

The Norwegian Radium Hosp, Univ of Oslo, Oslo, Norway

2540

Background: In an ongoing phase I/II trial advanced melanoma patients are vaccinated with autologous dendritic cells (DCs) transfected with RNA from the individual patient’s tumor. The objective is to make DCs present a broad spectrum of tumor-associated antigens and elicit immune response against tumor-associated proteins relevant to each individual patient. Methods: DCs are generated from monocytes obtained from peripheral blood cells (PBMCs). Monocytes are cultured with IL4 and GM-CSF for 5 days differentiating into immature DCs, transfected with tumour RNA by electroporation and cultured for 2 days with cytokines facilitating maturation. Each patient receives 4 weekly vaccines. One group are vaccinated intradermally, another group receive ultrasound guided intranodal vaccines. In vitro immunoassays (INF, ELISPOT, and T-cell proliferation) are performed on pre- and post-vaccination PBMCs. Presently 22 patients have received all 4 vaccines. Our ethics committee approved the study and consent was obtained in all subjects. Results: No serious adverse effects have been registred. In 9 out of 19 evaluable patients in vitro immunoassays have demonstrated immunological response, i.e. T-cell response specific for tumor-RNA transfected DCs in post vaccination samples. After additional booster vaccine, 3 patients demonstrated enhanced T cell response. Among the 9 in vitro responders one patient have demonstrated a mixed tumor response, with disappearance/reduction of metastatic lymph node and subcutaneous tumors and another developed vitiligo. The remaining patients have progressive disease. From the patient with a mixed tumor response 30 different CD4⁺ T-cell clones have been generated that proliferate after stimulation by RNA-transfected DCs, and not to the non-transfected DC controls. The immunoassays demonstrate that transfection of DCs with tumor-RNA results in protein production, and in presentation on HLA II on the DCs of new peptides encoded by the transfected mRNA. Conclusions: The strategy of vaccinating with RNA-transfected DCs functions indeed and elicit cellular immune responses. In some patients the immune response may have a beneficial clinical effect.

No significant financial relationships to disclose.

Abstract presentation from the 2005 ASCO Annual Meeting