Here, we tested their binding to purified targets, tumor cells, and lymphocytes and their functional properties on tumor cells in comparison with the clinically validated immunomodulatory mAbs targeting the same ICs, i.e. the anti-LAG-3 (relatlimab), anti-PD-L1 (atezolizumab), and anti-PD-1 mAbs (pembrolizumab), used alone or in combination with a control bi-specific tribody devoid of the immunomodulatory scFv, which contains instead an unrelated scFv derived from the anti-viral Palivizumab antibody (called 53 P). Here, CD274 is linked to neoplasm.