Adoptive T cell transfer therapy is one of the most promising cancer immunotherapeutic approaches. In order to provide adequate and efficient T cells for cancer treatment, T cells targeting specific cancer antigens are commonly generated in a dendritic cell (DC)-based ex vivo T cell priming system. A cancer/testis antigen, NY-ESO-1, is amongst the most immunogenic cancer antigens. It is expressed in various malignant tumors but not in normal tissues. Due to its restricted expression pattern and exceptionally strong immunogenicity, NY-ESO-1 is considered as a potential target for cancer immunotherapy. This study attempts to investigate the generation of NY-ESO-1 specific cytotoxic T lymphocytes (CTLs) in a DC-based ex vivo T cell priming system....[ Read more ]

Adoptive T cell transfer therapy is one of the most promising cancer immunotherapeutic approaches. In order to provide adequate and efficient T cells for cancer treatment, T cells targeting specific cancer antigens are commonly generated in a dendritic cell (DC)-based ex vivo T cell priming system. A cancer/testis antigen, NY-ESO-1, is amongst the most immunogenic cancer antigens. It is expressed in various malignant tumors but not in normal tissues. Due to its restricted expression pattern and exceptionally strong immunogenicity, NY-ESO-1 is considered as a potential target for cancer immunotherapy. This study attempts to investigate the generation of NY-ESO-1 specific cytotoxic T lymphocytes (CTLs) in a DC-based ex vivo T cell priming system.

Several factors including antigen, co-stimulation and cytokines may affect the generation of antigen specific CTLs in ex vivo T cell priming. Since NY-ESO-1 is a protein containing a complicated oligomeric structure, we first investigated the effectiveness of different oligomeric forms of the NY-ESO-1 antigen on CD8⁺ T cell immunogenicity. Second, we explored the functional role(s) of IL-7 in enhancing the generation of NY-ESO-1 specific CTLs in an ex vivo system. Finally, we examined the ability of IL-12 to enhance the generation of NY-ESO-1 specific CTLs ex vivo. For each part of the study, the effector function of generated NY-ESO-1 specific CTLs was evaluated through interferon-γ (IFN-γ) releasing assay and cytotoxicity assay. Results indicated that IL-12 could effectively enhance the generation of NY-ESO-1 specific T cells and IL-7 was capable of maintaining the survival of the primed T cells, whereas the alteration of NY-ESO-1 oligomeric structure was not a feasible way to augment the generation of NY-ESO-1 specific CTLs. In conclusion, the selection and administration of appropriate cytokines plays a critical role in the generation of NY-ESO-1 specific T cells ex vivo.