Dendritic cell based vaccination in combination with IL-2 as a treatment for advanced renal cell carcinoma patients: Results from a phase I/II trial

Abstract

2575 Background: Autologous dendritic cells (DC) pulsed with tumor-associated antigens as peptides or tumor lysate derived proteins can induce generation of cytotoxic T-cells in cancer patients. Survivin and telomerase are tumor-associated antigens overexpressed in renal cell carcinoma, and telomerase and survivin derived HLA-A2 binding peptides are able to induce effector T-cells cytotoxic to tumor cells. Tumor lysate can be generated from allogeneic renal carcinoma cell lines and has a natural high amount of antigens potentially enabling the induction of a polyclonal immune response against multiple targets on tumor cells. Methods: Twenty-two patients with progressive metastatic renal cell carcinoma were included and toxicity and efficacy of DC-based immunotherapy were evaluated. HLA-A2 positive patients were treated with mature autologous DCs pulsed with a broad panel of HLA binding telomerase and survivin peptides and PADRE; HLA-A2 negative patients received DCs pulsed with allogeneic tumor lysate and KLH. The vaccines were administered intradermally or intranodally weekly/biweekly ten times and repeated monthly until tumor progression. Patients received low dose IL-2 as an adjuvant. Immune response was monitored using ELISPOT assay. IL-6 and the biomarker YKL-40 were measured in serum using ELISA assay. Results: Vaccinations were well tolerated. 17/22 patients were evaluable and 10 patients had stable disease (SD) for up to 11+ months (range 2–11+ months). Interestingly, serum IL-6 increased in patients with progressive disease compared with a decrease in patients with SD. After vaccination mean values of YKL-40 were 91ng/ml in patients with SD and 208ng/ml in patients with PD. Immune monitoring is ongoing and preliminary data demonstrate that peptide specific CTLs are induced by the treatment. Conclusions: This pilot study demonstrates, that vaccination with autologous DCs pulsed with tumour antigens is safe and without severe toxicity. Disease stabilization was observed in half of the treated patients. Serum IL-6 and YKL-40 values might be useful parameters to predict clinical response during vaccination therapy. No significant financial relationships to disclose.