Purpose: 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.
Material And Methods: 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.
Results: 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.
Conclusions: 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.
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