Pre-clinical efficacy of the first glyco-humanized oncolytic polyclonal antibody (XON7) in onco-hematology

e14519 Background: Polyclonal antibodies pAb were shown to possess oncolytic properties a century ago with reported clinical responses. More recent pre-clinical models confirmed pAb efficacy though their ability to tackle complex target antigens. The emergence of escape variants could be minimized by multi-targeting of tumor cells with pAb, which would be more efficient than mAb at mediating effector functions for target destruction. However, the use of heterologous pAb is limited by their immunogenicity. Glyco-humanization (GH) solves this issue and allows to reconsider the potential of pAb in oncology. 3 GH-pAb have already been introduced in clinic in non-oncology settings, with a good safety profile. XON7 is a new GH-pAb targeting cancer cells. Methods: Complement dependent cytotoxicity (CDC) and apoptosis against various tumor cell lines and PBMC from healthy donors were tested with XON7 at increasing concentrations (6,25 µg/mL to 400 µg/mL) Specific binding to human tumors was assessed by immunochemistry on tissue micro-array (13 sections of original tumor, 13 healthy tissues). Cross-cancer activity was evaluated on biopsies from patients with solid tumor or blood cancer: CRC (n=63), NSCLC (n=30), Osteosarcoma (n=4), pancreatic (n= 48), GIST (n=2), AML (n=10), DLBCL (n=7). Xenograft mice model: XON7 efficacy was tested in several sub cutaneous xenograft models in NMRI nude mice (n=10 per group) using A549: non-small-cell lung cancer, HCT-116: colon cancer, LnPac: prostate cancer, KMS-12-BM: myeloma, T1301: T cell lymphoma. Treatments (35mg/kg, twice a week) were given for 4 weeks once the tumor reached 50 mm 3 . Results: XON7 induced specific human tumor cell lines CDC (IC50=50ug/mL) and apoptosis (IC50= 100ug/mL) up to 100% of the cells, without cross-reactivity with healthy human cells. XON7 targets several patients’ tumoral tissues. In vivo, XON7 induces a significant reduction of tumor growth ranging from 40 to 90% across all tested tumors. Conclusions: Immunotherapy with XON7 could be a novel therapeutic approach to fight solid tumors and hematological malignancies. [Table: see text]