Autologous tumor cell vaccination with PF-3512676 (CPG 7909) and GM-CSF followed by subcutaneous PF-3512676 and IFN-alpha for patients with metastatic renal cell carcinoma

Abstract

2530 Background: Metastatic renal cell carcinoma (RCC) has a poor prognosis with a 5-year survival of less than 10%. Non-specific immunotherapy, e.g. IL-2 and IFN-α achieves responses in 10–30% of patients at the cost of relatively high toxicity. Tumor vaccination has shown great promise in a variety of cancers, particularly in the adjuvant setting. Studies in metastatic setting are suitable to identify the best adjuvants and to optimize vaccination schedules. CpGs are synthetic oligonucleotides that have been shown to have superior immunogenicity in animal and human vaccination studies (Hepatitis B). Besides its positive effect on the specific immune response, CpGs also stimulate the innate immune system. We initiated a phase I/II trial to investigate the potentials of CpG in the treatment of metastatic RCC. Methods: Nephrectomized patients with progressive metastatic RCC were vaccinated with autologous tumor cells (ATC) derived from the primary tumor or metastases. Vaccines consisted of irradiated ATC, PF-3512676 and GM-CSF. The first three induction vaccinations were given weekly followed by subcutaneous administration of IFN-α (6 MIU, TIW) and PF-3512676 (8 mg bi-weekly). After 3 months tumor evaluation was performed and in case of a remission or stable disease patients continued with 3 monthly vaccinations and PF-3512676 /IFN-α. Blood was collected for immunomonitoring and DTH responses against ATC were measured before and after vaccination. Results: Preparation of vaccines was successful in 88% of the patients. Twelve patients were included and treated according to the protocol. Treatment was well tolerated. At the vaccination site we observed erythema and induration. Some patients experienced flu-like symptoms, including fever and fatigue. In all patients we observed only after vaccination a DTH response (> 10 mm) against ATC, suggestive for a specific antitumor response. Three patients (25%) achieved a partial response (durations 6, 4+, 4+ months) and 2 patients (17%) stable disease (3 months). Conclusions: This new combined immunotherapy is tolerable, safe, and immunogenic. Moreover, it can produce tumor responses in advanced RCC. No significant financial relationships to disclose.