Abstract 2738: XON7, a new Glyco-Humanized Polyclonal Antibody, first in class immunotherapy against several solid tumors
Authors: Carine Ciron, Gwenaelle Evanno, Pierre Morice, Pierre-Joseph Royer, Françoise Shneiker, Odile Duvaux, Bernard Vanhove, Firas Bassissi
Journal: Cancer Research (2024)

Abstract Introduction: Cancer immunotherapy has recently generated much excitement after the success of the immunomodulating anti-CTLA-4 and anti-PD-1 antibodies against various types of cancers. However, for many cancers, there is still a lack of effective treatment that can result in long-term cancer-free survival and lower metastatic and relapse risks. The emergence of cancer resistance could be minimized by drug combination or by multi-targeting of tumor cells. Polyclonal antibodies can target several tumor-associated antigens simultaneously and would be more efficient than a conventional mAbs. Here we evaluate the safety and efficacy of XON7, a first in class glyco-humanized polyclonal antibody (GH-pAb), in cancer preclinical models. Material and Methods: XON7 ability to induce Complement Dependent Cytotoxicity (CDC) and apoptosis was tested in a panel of cancer cell lines and PBMC. XON7 was also evaluated in sphere formation assay to predict its effects on cancer resistant. Specific binding to human tumors and healthy tissues was assessed by immunochemistry on tissue micro-array. Cross-cancer activity was evaluated on biopsies from patients with solid tumor such as CRC, NSCLC, osteosarcoma, and breast cancers. In vivo XON7 efficacy was evaluated in NMRI nude mice using A549: NSCLC, HCT-116: colon cancer, LNCaP: prostate cancer and MDA-MB-231: breast cancer cells. A human NSCLC chorio-allantoic membrane (CAM) model was used to evaluate the efficacy of XON7 + anti PD-1 on tumor growth and metastasis. Pharmacokinetics and safety of this drug were assessed in marmoset after single and repeated IV dosing up to 60mg/kg. Results: XON7 showed a potent in vitro antitumor activity in a panel of cancer cell lines, it induced specific tumor cell CDC (EC50=50ug/mL) and apoptosis (IC50= 100ug/mL). it was able to kill up to 100% of the cancer cells without affecting PBMC. In addition, it induced a striking decrease of tumor sphere formation in HCT116, A549 and MDA-MB-231 cancer cell lines. XON7 showed preferential recognition of tumor cells as compared to normal cells, it demonstrated cross-reaction to tumor patient biopsy without staining of the healthy tissues. In vitro XON7 potency was translated into in vivo efficacy in different mice xenograft models. XON7 induced a significant reduction of tumor growth ranging from 40 to 90% across several tested tumors. Furthermore, it showed, significant increase of anti-tumor response rate and decrease of metastasis when it is associated with anti PD-1 in vivo CAM model (&amp;gt;90%, p=0.001). XON7 was also characterized by high tolerance and satisfactory exposure in marmoset. Conclusion: Based on its safe toxicity profile and potent activity, XON7 appeared as a novel and promising cancer immunotherapy to fight against recurrent solid tumor, it is now aimed to reach clinical development, FIH in patients is planned to start before the end of 2023. Citation Format: Carine Ciron, Gwenaelle Evanno, Pierre Morice, Pierre-Joseph Royer, Françoise Shneiker, Odile Duvaux, Bernard Vanhove, Firas Bassissi. XON7, a new Glyco-Humanized Polyclonal Antibody, first in class immunotherapy against several solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2738.