Telomerase Pulsed Dendritic Cells for Immunotherapy for Renal Cell Carcinoma

Abstract

Renal cell carcinoma (RCC) is known for its immunological susceptibility. Unfortunately RCC lacks specific tumor antigens for the induction of specific immunotherapy. We investigated the role of telomerase as a tumor antigen and pulsed dendritic cells (DCs) as antigen presenting cells with an immunogenic peptide from telomerase. DCs and immunological effector cells, that is cytokine induced killer (CIK) cells, from patients with RCC or healthy donors were generated. CIK cells were co-cultured with telomerase peptide pulsed DCs. CIK cells were tested for cytotoxic activity against primary cultures. Using the dimer technique we determined the percent of telomerase specific T cells. Activation status was identified using interferon-gamma secretion assay. After pulsing DCs with telomerase peptide co-cultured CIK cells had a significant increase in cytotoxic activity against tumor cells compared with CIK cells without co-culture, that is 100% at an effector-to-target ratio of 60:1 vs 41.7% (p <0.05). Using a complete autologous model with immunological cells derived from patients with metastatic RCC we were able to induce cytotoxicity against autologous, telomerase positive primary cell cultures. We could detect 2.4% telomerase specific effector cells after co-culture with peptide pulsed DCs, which secreted interferon-gamma after re-stimulation. Telomerase could serve as a specific tumor associated antigen for RCC. The presentation of telomerase peptide by DCs to lymphocytes allows the generation of antigen specific cytotoxic effector cells.