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…

Generation of cytotoxic T-cell responses with synthetic melanoma-associated peptidesin vivo: Implications for tumor vaccines with melanoma-associated antigens

Peptide epitopes derived from differentiation antigens of the melanocyte lineage have been identified in human melanomas and normal cultured melanocytes as targets for MHC-restricted cytotoxic T lymphocytes (CTL). Characterization of multiple CTL-defined antigenic determinants and the presence of corresponding precursor CTL open perspectives for the development of antigen-based vaccines. In the present study, we determined the CTL reactivity against melanoma-associated peptides derived from Melan A/MART-1, tyrosinase and gp100/Pmel17 in 10 HLA-A2+ melanoma patients and 10 healthy individuals. Then, we examined the immunological effects and toxicity of intradermal inoculation of synthetic me…

Docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) for resectable esophagogastric cancer: Updated results from multicenter, randomized phase 3 FLOT4-AIO trial (German Gastric Group at AIO)