Abstract 701: Immunogenicity risk assessment and mitigation tools

Abstract

Abstract New immuno-oncology mAbs or agents with other structures have revolutionized treatment options for several malignancies in the past few years, and more are currently being evaluated in the clinic. The development of new therapeutics comes with a series of challenges and questions, of which one is the risk for unwanted immunogenicity which can lead to decreased efficacy and safety concerns. Today, both in silico and in vitro preclinical tools are available to identify early on therapeutic candidates with a high immunogenicity risk potential. Additionally, certain tools can be used to mitigate the immunogenicity potential, and thus improve and accelerate therapeutic drug development and reduce the number of clinical failures. Often used as a first step is an in silico T cell epitope prediction algorithm such as NetMHCIIpan which can be used to assess and compare the immunogenic potential of the lead candidates and guide de-immunization strategies. Further monitoring of the immunogenic risk can be performed using different in vitro assays: a peptide screen assay, to enable the exclusion of immunogenic peptides and the inclusion of low risk sequences; a dendritic cell activation assay to assess immunogenicity signals for the whole product; the MAPPs or MHC Associated Peptide Proteomics, assay to follow uptake, processing and presenting of biotherapeutics by dendritic cells and identify specific regions of concern, and; in vitro T cell proliferation and activation assays to determine and rank the immunogenic risk of the test proteins. The compilation of the different datasets and translation of the results into a comprehensive risk management plan, allows selection of the best candidates to move forward into humans, deimmunization of test candidates and identification and discontinuation of the high-risk candidates as early as possible. Citation Format: Amin Osmani, Sofie Pattijn, Jana Schockaert, Aurélie Mazy, Chloé Ackaert. Immunogenicity risk assessment and mitigation tools [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 701.