In vitro activation of cytotoxic T-lymphocytes by hTERT-pulsed dendritic cells

Abstract

Multiple myeloma has been considered a weakly immunogenic malignancy that can cause profound defects in the immune system. An important issue for the immunotherapy of myeloma is the identification of appropriate tumor-associated antigens (TAAs). Recently, hTERT (human telomerase reverse transcriptase) was detected on a majority of human malignancies. In the studies reported here, we studied antigen-specific and HLA-A2-restricted cytotoxic activity against an ARH77 myeloma cell line in vitro. An HLA-A2-specific hTERT-derived nonapeptide (⁵⁴⁰ILAKFLHWL⁵⁴⁸) was used as a TAA. Myeloma-specific cytotoxic activity of hTERT-reactive cytotoxic lymphocytes (CTLs) was established by repeated stimulation of the CTLs via dendritic cells loaded with hTERT-derived nonapeptide. These studies were able to demonstrate that hTERT-reactive T-lymphocytes can be identified and expanded using relatively simple in vitro techniques consisting of antigen-specific stimulation, immunomagnetic sorting, and then induction of rapid expansion.

Keywords::

• hTERT
• TAA
• multiple myeloma

Acknowledgment

This study was graciously supported with funding from grants MSMT LC06027 and IGA MZCR 1A8709-5.

Declaration of interest: The authors report no conflicts of interest and are fully responsible for the content and writing of this paper.