IgG-based anti-cancer therapies have achieved promising clinical outcomes, but, especially for patients with solid tumors, response rates vary. IgE antibodies promote distinct immune responses compared to IgG and have shown anti-tumoral pre-clinical activity and preliminary efficacy and safety profile in clinical testing. To improve potency further, we engineered a hybrid IgE-IgG1 antibody (IgEG), to combine the functions of both isotypes. Two IgEGs were generated with variable regions taken from trastuzumab (Tras IgEG) and from a novel anti-HER2 IgE (26 IgEG). Both IgEGs expressed well in mammalian cells and demonstrated IgE-like stability. IgEGs demonstrated both IgE and IgG1 functionality