0000000000148185
AUTHOR
Dirk Jung
Strong immunogenic potential of a B7 retroviral expression vector: generation of HLA-B7-restricted CTL response against selectable marker genes.
The stimulation of a specific immune response is an attractive goal in cancer therapy. Gene transfer of co-stimulatory molecules and/or cytokine genes into tumor cells and the injection of these genetically modified cells leads to tumor rejection by syngeneic hosts and the induction of tumor immunity. However, the development of host immune response could be either due to the introduced immunomodulatory genes or due to vector components. In this study, human renal cell carcinoma cell lines were modified by a retrovirus to express the co-stimulatory molecule B7-1 together with the hygromycin/thymidine kinase fusion protein (HygTk) as positive and negative selection markers. These B7-1-transd…
Induction of immunogenicity of a human renal-cell carcinoma cell line byTAP1-gene transfer
Reduced expression of the major-histocompatibility-complex(MHC)-class-I antigens has been demonstrated in renal-cell carcinoma (RCC), and appeared to be associated with deficiencies in the expression and function of different components of the MHC-class-I-antigen-processing pathway and poor recognition by cytotoxic T-lymphocytes (CTL). In order to investigate the role of peptide transporters for the immunogenic phenotype of RCC, tumor cells were stably transfected with the human TAP1A gene. While the TAP1 transfectants showed heterogeneous TAP1-transgene expression pattern of mRNA and protein, high TAP1 expression and a TAP-controlled increase in MHC-class-I surface expression could be achi…
Gene transfer of the Co-stimulatory molecules B7-1 and B7-2 enhances the immunogenicity of human renal cell carcinoma to a different extent.
Stimulation of a specific antitumour immune response with recruitment and induction of T-cell effector functions represents an attractive concept in human cancer therapy. Different cytokines and the B7 co-stimulatory molecules are both able to provide proliferation and activation signals for T cells. In the present study, we first demonstrated the absence of both B7-1 and B7-2 expression in human renal cell carcinoma (RCC) cell lines. The lack of B7 expression was associated with a low or absent proliferative response of allogeneic and autologous T cells upon stimulation with tumour cells. In order to investigate the role of B7-1 and B7-2, the human RCC cell line, MZ1257RC, which expresses …