The invention relates generally to multispecific polypeptides having constrained CD3 binding. In some embodiments, the multispecific polypeptides contain non-cleavable linkers that do not contain a substrate recognition site specific to cleavage by a protease. Also provided are methods of making and using these multispecific polypeptides in a variety of therapeutic, diagnostic and prophylactic indications.本發明大體上係關於具有經受限CD3結合的多重特異性多肽。於一些實施例中,該等多重特異性多肽含有非可裂解連接子,該等連接子不含有對藉由蛋白酶裂解具特異性之受質識別位點。本發明亦提供製備及使用此等多重特異性多肽於各種治療性、診斷性及預防性適應症中之方法。