Vaccinations with RNA coding for tumor associated antigens in advanced RCC patients—A phase I/II study

Abstract

3017 Background: RCC is recognized as an immunogenic tumor and several TAA are known to be widely expressed on RCC. In previous experiments intradermal vaccination of naked RNA in mice showed that this approach leads to expression of the corresponding protein and induction of a protective antitumor immunity. Methods: Based on these results we conducted a phase I/II trial to evaluate feasibility, safety and efficacy as well as immunological responses of RNA vaccination in patients with metastatic RCC. Vaccination was performed with mRNA encoding for TAA using 2 different treatment arms. Eligibility criteria included bidimensionally measurable lesions, age 18 to 79 years and a 6 week interval to last therapy. In vitro transcribed RNA was generated using plasmids coding for the TAA MUC1, CEA, Her-2/neu, telomerase, survivin and MAGE-1. Vaccinations were performed intradermally on days 1, 14, 28 and 42 in arm A and on days 0–3, 7–10, 28 and 42 in an intensified arm B. Subsequently vaccinations were repeated monthly until documented tumor progression. On the day following RNA vaccination GM-CSF was applicated s.c. Results: 30 patients aged 36 to 79 years were enrolled in this study, 14 in arm A and 16 in arm B. All patients had progressive disease and had received previous therapy. Treatment was well tolerated with no severe side effects. In arm A 1 patient showed tumor shrinkage of pulmonary metastasis. 42.9% of patients survived more than 24 months with a median survival of 15.1 months for the whole population. 7 of 14 patients showed stable disease (RECIST) at analysis on day 42. 85.7% of these patients survived more than 24 months (after first vaccination). In the intensified arm B tumor shrinkage was observed in 2 patients with 52.9% surviving more than 2 years. The median survival for the whole population was 20 months. 12 of 17 showed stable disease on d42. 90% of these patients survived more than 2 years (after first vaccination). In ongoing ELISPOT assays CD4+ and CD8+ T cell induction could be shown for several TAA. Furthermore, induced cyctotoxic T cells lysed HLA matched tumor cells in an antigen specific manner. Conclusions: This study demonstrates that vaccination with RNA coding for TAA can be effective in the treatment of RCC patients and induces clinical and immunological responses. No significant financial relationships to disclose.