Traditional monoclonal antibodies and bispecifics targeting multiple antigens or epitopes have been showing great promise for treatment of cancer. However, managing unwanted immunogenicity has become a challenge in the development cycle of these promising therapeutics as there is a trend towards higher unwanted immune responses compared with classical monoclonal antibodies. In vitro assays using human primary immune cells can be used to assess the risk of induction of a cytokine release storm or induction of unwanted immunogenicity. For the latter, T cell activation and proliferation assays can be used to assess and predict an unwanted immune response and avoid induction of anti-drug antibodies later on. In order to achieve reliable and consistent results, high quality primary immune cells should be used in combination with sensitive fit-for-purpose in vitro assays. 

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