The therapeutic landscape in breast cancer has benefited from the development of variate antibody-based therapies. Yet, pre-clinical models capable of recapitulating the complex crosstalk within the tumor microenvironment (TME) are needed to properly address the effect of such therapies. In this work, we devised cell models able to accommodate different cell populations (3D-3), by adding stromal and immune components to multicellular tumor spheroids. The models were microencapsulated in alginate and kept under stirred conditions, to recreate critical hallmarks of the TME.