580P AT1412, a patient-derived CD9 antibody promotes tumour immune infiltration and induces tumour rejection

Abstract

Methods: For in vitro cytotoxicity assays, MORAb-109 was evaluated in 5-day assays using various tumor cell lines. Tumor-cell line-derived and patient-derived in vivo tumor effiicacy studies were performed in immunocomprimized mice, Treatment was done via i.v. injection when tumors reached w 150-200 mm 3 . PK assays were performed in tumor-bearing mice, with detection of ADC by ligand-binding assay. Stability assays were performed in both plasma and serum from various species using a DAR-sensitive biolayer inferometry binding assay.Results: In vitro, MORAb-109 demonstrated selective cytotoxicity on a number of mesothelin-expressing tumor cell lines compared with non-expressing lines, with an improved specificity ratio compared with a competitor ADC. MORAb-109 exhibited dose-dependent anti-tumor activity in vivo, with regression observed in multiple tumor cell line and patient-derived xenograft models, including models with heterogeneous mesothelin expression. The ADC demonstrated good stability in matrix from multiple species in vitro, with limited (< 20%) payload release after 10-day incubation.Conclusions: Based on these findings, MORAb-109 is being considered for further development as a targeted therapy for mesothelin-expressing tumors.Legal entity responsible for the study: Eisai Inc.

CD9, a tetraspanin target for cancer therapy?

“…177,198,199 A promising divalent anti-CD9 Ab is the AT1412 clone isolated from survivors of stage IV metastatic melanoma that did not induce platelet aggregation or thrombosis. 198,200,201 Although not experimentally evaluated, it is conceivable (and perhaps advantageous) that the development of bispecific Abs targeting CD9 and another tumor-associated antigen or one of its interacting partners (e.g. EWI-2, 24 EWI-F, 202 integrins), notably those involved in cell adhesion or migration, could improve the specific targeting and potentially interfere with cancer progression.…”