Dysfunctional T cells, which are commonly observed in cancer patients, decrease the overall function of cytotoxic T lymphocytes (CTLs) in controlling tumor progression, resulting in a poor response to immunotherapy. Adoptive T cell transfer replaces the defective T cells in cancer patients with in vitro activated T cells. The overall therapeutic efficacy of in vitro activated tumor antigen-specific CTLs largely depends on the choice of tumor antigens and the proper function of antigen presenting cells (APCs), especially dendritic cells (DCs). Tumor antigens usually cannot elicit strong immune response, probably due to immune tolerance to self-antigen. In addition, the function of DCs is limited by several factors, including differentiation approaches, antigen loading efficiency, and mat...[ Read more ]

Dysfunctional T cells, which are commonly observed in cancer patients, decrease the overall function of cytotoxic T lymphocytes (CTLs) in controlling tumor progression, resulting in a poor response to immunotherapy. Adoptive T cell transfer replaces the defective T cells in cancer patients with in vitro activated T cells. The overall therapeutic efficacy of in vitro activated tumor antigen-specific CTLs largely depends on the choice of tumor antigens and the proper function of antigen presenting cells (APCs), especially dendritic cells (DCs). Tumor antigens usually cannot elicit strong immune response, probably due to immune tolerance to self-antigen. In addition, the function of DCs is limited by several factors, including differentiation approaches, antigen loading efficiency, and maturation stage. In principle, any approach that can enhance the immunogenicity of the tumor antigens or improve the function of DCs leads to the creation of more effectively adoptive T cell transfer therapy.

MAGE-A1, the first identified cancer/testis antigen, is frequently expressed in liver, esophageal and lung cancers, seminoma and melanoma but not in normal tissue except the testis. MAGE-A1 has been used in immunotherapy for certain types of cancers such as hepatocellular carcinoma (HCC) and melanoma. However, immunotherapy with human MAGE-A1 has proven unsatisfactory. In this study, three approaches were used to enhance the activity of MAGE-A1 targeting CTLs: 1) enhancing the antigen expression and presentation of DCs by using adenovirus vectors, 2) improving the immunogenicity of MAGE-A1 by using xenogeneic homologous MAGEs, and 3) comparing interferon-α induced DCs to interleukin-4 induced DCs for their ability to prime MAGE-A1 specific CTLs. Results in this study demonstrated that all three enhanced the activity of MAGE-A1 targeting CTLs and had the potential to be applied to enhancing immunotherapy for other tumor antigens.