Bispecific antibodies enhance tumor-infiltrating T cell cytotoxicity against autologous HER-2-expressing high-grade ovarian tumors.

ABSTRACT: Epithelial ovarian cancer displays the highest mortality of all gynecological tumors. A relapse of the disease even after successful surgical treatment is a significant problem. Resistance against the current platinum-based chemotherapeutic standard regime requires a detailed ex vivo immune profiling of tumor-infiltrating cells and the development of new therapeutic strategies. In this study, we phenotypically and functionally characterize tumor cells and autologous tumor-derived ?? and ?? T lymphocyte subsets. Tumor-infiltrating (TIL) and tumor-ascites lymphocytes (TAL) were ex vivo isolated out of tumor tissue and ascites, respectively, from high-grade ovarian carcinoma patients (FIGO-stage IIIa-IV). We observed an increased ?? T cell percentage in ascites compared to tumor-tissue and blood of these patients, whereas CD8+ ?? T cells were increased within TAL and TIL. The number of V?1 and non-V?1/V?2-expressing ?? T cells was increased in the ascites and in the tumor tissue compared to the blood of the same donors. Commonly in PBL, the V?9 chain of the ?? T cell receptor is usually associated exclusively with the V?2 chain. Interestingly, we detected V?1 and non-V?1/V?2 T cells co-expressing V?9, which is so far not described for TAL and TIL. Importantly, our data demonstrated an expression of human epidermal growth factor receptor (HER)-2 on high-grade ovarian tumors, which can serve as an efficient tumor antigen to target CD3 TIL or selectively V?9-expressing ?? T cells by bispecific antibodies (bsAbs) to ovarian cancer cells. Our bsAbs efficiently enhance cytotoxicity of TIL and TAL against autologous HER-2-expressing ovarian cells.

SUBMITTER: Oberg HH 

PROVIDER: S-EPMC7318294 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature