Abstract 2737: LIS22, a first in class polyclonal antibody immunotherapy in T cell blood cancers

Abstract Background: Several approaches such as antibody drug conjugate (ADC), chimeric antigen receptor T cells (CAR-T) and recently bispecific antibodies are being introduced as innovative weapon in B-Cell lymphoma treatment. In the opposite, very limited therapeutic options are available for the treatment of rare refractory T cell malignancies such as PTCL. The 5-year survival rate of PTCL is lower than 30% according to the recent clinical data. Developing new effective treatment strategies for PTCL is an urgent problem. LIS22, is a first in class glyco-humanized polyclonal antibody (GH-pAb), targeting multiple tumor-associated antigens simultaneously. In this study, we characterized the safety and efficacy of LIS22 in preclinical models of T cell malignancies. Material and Methods: LIS22 ability to induce Antibody-Dependent Cell Cytotoxicity (ADCC), Antibody-Dependent Cellular Phagocytosis (ADCP), Complement Dependent Cytotoxicity (CDC), and apoptosis was tested in a panel of hematologic malignancy cell lines and peripheral blood mononuclear cell (PBMC). To assess the targeting and recognition of LIS22 in PTCL patients, we evaluated the immunolabelling of LIS22 on patients’ biopsies (n=119) using tissue microarray. LIS22 efficacy in vivo were evaluated in NMRI nude mice and SRG rats using T1301 and Jurkat cancer cell lines. Pharmacokinetics and safety of this drug were assessed in cynomolgus monkeys after single and repeated IV dosing up to 50mg/kg. Results: LIS22 acts via several mechanisms, at 30µg/ml, it induced cytotoxicity via CDC (in 70%), ADCP (in 49%), ADCC (in 41%) and apoptosis (in 30%) of HPB-ALL human T blood cancer cell line but not in PBMC. LIS22 showed a potent in vitro antitumor activity in a panel of hematologic malignancy cell lines, it induced specific tumor cell CDC (EC50=41.4±28.9µg/mL). In both CDC and apoptosis cytotoxicity assays, LIS22 displayed a significantly higher potency on T cell blood cancers and no toxicity on healthy blood cells compared to PTCL clinically active drug Alemtuzumab (Anti-CD52). It was able to kill up to 100% of the cancer cells without affecting PBMC. In immunolabeling assay, LIS22 demonstrated cross-reaction to PTCL patient biopsy (staining up to 93%). In vivo efficacy studies in different mice and rat xenograft models, LIS22 induced a significant reduction of tumor growth up to 90% across several tested tumors. LIS22 was also characterized by high tolerance profile and satisfactory exposure in monkeys after repeated dosing (up to 250mg/kg of cumulative dose). Conclusion: LIS22 appeared as a novel and promising cancer immunotherapy against T Cell hematologic malignancies. It has already been administered to human in another indication and showed a satisfactory PK and safety profile (no signs of immunotoxicity or systemic cytokine release). LIS22 is now ready to enter Phase I/II in the coming months for the treatment of peripheral T cell lymphoma (PTCL). Citation Format: Carine Ciron, Francoise Shneiker, Ophélie Dauphouy, Juliette Rousse, Pierre-Joseph Royer, Gwenaelle Evanno, Odile Duvaux, Firas Bassissi. LIS22, a first in class polyclonal antibody immunotherapy in T cell blood cancers [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 2737.