Hla-A0201-Positive, Il-7/B7.1-Cotransfected Allogeneic Tumor Cells As A Vaccine In Metastatic Renal Cell Cancer-A Clinical Phase-I Trial

3072 Background: Tumor vaccination remains a promising experimental approach in RCC. HLA-A0201-restricted T cell immunity against RCC is well established. RCC26 is an allogeneic HLA-A0201+ human RCC cell line, a T cell clone specifically recognising RCC26 and other RCC in the context of HLA-A0201 has previously been generated, the TCR of this T cell clone was characterised. Furthermore, IL-7/B7.1 cotransfected tumor cells are a potent vaccine in animal models. Methods: RCC26 was transfected with pKEx-IL-7-IR-B7 coding for human IL-7 and B7.1 (CD80). 10 HLA-A0201+ patients with metastatic RCC and disease progression under cytokine therapy were included. 10 vaccinations with 2.5–40x106 gene-modified irradiated tumor cells which had been produced under GMP conditions were performed s.c. over 22 weeks. Primary endpoints of the study were feasibility, safety and immunological response, secondary endpoint was clinical response. The protocol was approved by the ethics committee, all patients gave informed consent. Results: Gene-modified RCC26 cells produced IL-7 (3.4 ng/106 cells/24h), more than 90% of the cells were CD80+. Vaccination was feasible and safe with no severe toxicity. Local DTH-reactions were observed in 4 patients. Skin biopsies of the vaccination site showed lymphocytic infiltrates dominated by CD4+T cells. In 8 patients vaccination induced HLA- and /or antinuclear antibodies without clinical signs of autoimmunity. Analysis of the T cell response against RCC-associated antigens is under way. No partial or complete responses could be documented. However, 50% of the patients had stable disease with the longest TTP being 69 weeks. Mean TTP in our cohort was 25 weeks (range 4 to 69 weeks). Conclusion: Our results show that vaccination with an allogeneic gene-modified tumor cell line is feasible and safe. Stable disease lasting up to 69 weeks in a substantial proportion of patients suggests immunological activity of the vaccine. Vaccination of patients with a low tumor burden is a promising strategy for the future, i.e. after surgery or treatment with novel multi-kinase inhibitors. No significant financial relationships to disclose.