We demonstrate here that this novel immuno-tBid induces the specific destruction of HER2-overexpressing SOSP-9607-E10 cells through the release of cytochrome C. These results suggest that the novel immuno-tBid with a minimized exogenous fragment could represent a competitive approach for the treatment of HER2-positive osteosarcoma.
In conclusion, as our study showed amplification of HER2/neu oncogene in low-grade osteosarcoma, we assume that expression of HER2/neu is not a poor prognostic factor in low-grade osteosarcoma.
We initially studied 21 cases of osteosarcoma by FISH analysis (using a technique that included a probe for chromosome 17), 11 of which had their HER-2/neu gene amplification status previously reported.
The titer of rrVSV on SKBR3 cells, a human breast cancer cell line which highly expresses erbb2 was 3.1 x 10(7)/ml compared with a titer of 7.3 x 10(5)/ml on 143 cells, a human osteosarcoma cell line which does not express erbb2.
Studies on ErbB receptors in osteosarcoma have focused on HER-2 and have produced conflicting results with few studies evaluating the expression of the epidermal growth factor receptor (EGFR).
Further, top three core targets of FN anti-OGS were determined as oestrogen receptor 1 (ESR1), tumour protein p53 (TP53), receptor tyrosine-protein kinase erbB-2 (ERBB2) respectively.
Expression of the e23sFv-PEA II-Bid Delta1-60 gene suppressed tumor growth, significantly prolonged animal survival and inhibited metastasis, thereby suggesting it may represent a competitive approach to treating HER2/neu-positive osteosarcoma.
Our data showed that the immuno-casp-6 can specifically recognize HER2-overexpressing osteosarcoma cells, can also promptly attack their nucleus and induce apoptotic death, suggesting the potential of this strategy for the treatment of human HER2-overexpressing tumors.
The adoptive transfer of HER2-specific T cells caused regression of established osteosarcoma xenografts in locoregional as well as metastatic mouse models.
We demonstrate that canine OS is positive for HER2, and that canine T cells expressing a HER2-specific CAR with human-derived transmembrane and CD28.ζ signaling domains recognize and kill HER2(+) canine OS cell lines in an antigen-dependent manner.
The presence of increased levels of ErbB2 in osteosarcoma was significantly associated with the increased probability of event-free (72.2% v. 45.6% at 5 years, P = 0.03) and overall survival (79.7% v. 58.2% at 5 years, P = 0.03).
However, the role of EGFR and HER-2 expression in osteosarcoma survival remains controversial and no previous study has simultaneously investigated the association of the expression of all the four HER family members with the prognostic significance of osteosarcoma.
We conclude that the cell surface expression of Her-2 and EGFR and the nuclear localization of the activated p80 fragment of Her-4 suggest that all three may be contributing to osteosarcoma pathogenesis.