Intradermal RNA-Vaccination of Patients with Metastatic Renal Cell Carcinoma.

Background: The use of in vitro transcribed RNA isolated from tumor cells or coding for defined tumor associated antigens was shown to be a very powerfull method to generate antigen specific T cells upon transfection into dendritic cells (DC). More recently it was demonstrated in a mouse model that application of RNA intra dermaly can elicit both, CD8 and CD4 mediated immune responses. Furthermore, in Her-2-neu transgenic mice vaccinations with naked RNA were able to elicit a specific immune response in vivo and delay the development of breast cancer in treated animals. Based on these results we analyzed the clinical and immunological responses in patients with metastatic renal cell carcinoma (RCC) vaccinated with mRNA encoding for tumor associated antigens (TAA) using two different treatment arms.

Methods: In vitro transcribed RNA was generated using plasmids coding for the tumor antigens MUC1, CEA, Her-2/neu, telomerase, survivin and MAGE-1. RNA coding for HbsAg and Influenza matrix protein were included as controls. Vaccinations were performed intradermally on day 1,14, 28 and 42 in a first group of patients and on day 0–3, 7–10, 28 and 42 in a second group (intensified arm). Vaccinations were repeated afterwards monthly until tumor progression. One day after each RNA injection patients additionally received 1 injection of GM-CSF (250 μg) sc. The enhancement of T cell precursor was monitored using IFN-g ELISPOT and tetramer staining..

Results: 25 patients were included in this study. In 3 patients regression of metastases was induced and 6 patients had a stabilization of the disease. Specific CD8 and CD4 T cell responses in vivo were detected in the first analyzed patients. The treatment was well tolerated with no severe side effects. In most cases erythema and induration were observed after injections of GM-CSF. One patient developed an allergic exanthema after GM-CSF application.

Conclusions: This study demonstrates that intradermal RNA-vaccination can be effective in the treatment of metastatic RCC and induces clinical and immunological responses.