MT110 is a T cell-engaging, EpCAM/CD3-bispecific BiTE antibody that is currently being tested in a dose-escalating clinical phase 1 study in gastrointestinal and lung cancer patients. MT110 has shown high potency of redirected lysis in cell-based assays at picomolar concentrations.

Previous studies with MT110 have shown that subcutaneous (s.c.) pancreatic tumor formation can be delayed in NOD/SCID mice when human tumor cells are mixed prior to inoculation with human peripheral blood mononuclear cells (PBMC) at a ratio of 1:2. Likewise, MT110 is able to eradicate s.c.-implanted human metastatic tissue (<80 mm3) freshly dissected from ovarian cancer patients. In this model, the only source of effector cells were tumor-resident T cells from the respective patient sample.

Here we have further explored in a new NOD/SCID mouse model the anti-tumor activity of MT110 on established s.c. tumors derived from the human pancreas cancer cell line Aspc1. Effector cells, human peripheral T cells, were expanded ex vivo in the presence of T cell mitogens. NOD/SCID mice were reconstituted with human T cells by intraperitoneal (i.p.) injection once the tumors had reached at least 150 mm3. Following adoptive transfer, human T cells were detected in the peripheral blood of mice for up to 6 days. Tumor-bearing mice were treated for 28 days with 350 µg MT110/kg (approx. 3 µg MT110/mouse) by either daily i.v. bolus injection or continuous i.p. infusion using Alzet osmotic pumps.

With the onset of MT110 treatment by either route, Aspc1 tumors of approx. 300 mm3 started to shrink. After two weeks, tumors in all MT110-treated mice were less than

50 mm3, and 3 out of animals 11animals were completely free of tumor. In contrast, all tumors in vehicle control mice had reached an average size of 500 mm3 during this period. At the end of the study after 8 weeks and 2.5 weeks after last dosing, 3 out of 11 animals remained tumor-free. Among the remaining eight tumor-bearing animals, all showed tumor regression 38-40 days after start of the study. Our data show that established tumors grown can be eradicated by BiTE antibody MT110 by engaging initially extra-tumoral human T cells. This indicates that cancer therapy with MT110 and other BiTE antibodies in development may not solely rely on tumor-resident T cells. Moreover, MT110 may have activity against pancreatic cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2433.