The present invention is directed toDA x CD3 Binding Moleculescomprising a vCD3-Binding Domain, which comprises a CDRH1 Domain, a CDRH2 Domain, a CDRH3 Domain, a CDRL1 Domain, a CDRL2 Domain, and a CDRL3 Domain, at least one of which differs in amino acid sequence from the amino acid sequence of the corresponding CDR of a rCD3-Binding Domain, wherein the DA x CD3 Binding Molecule comprising such vCD3-Binding Domain exhibits an altered affinity for CD3, relative to aDA x CD3 Binding Moleculecomprising such rCD3-Binding Domain. The invention particularly concerns to suchDA x CD3 Binding Moleculescomprising a vCD3-Binding Domain which exhibit reduced affinity for CD3 and are capable of mediating redirected killing of target cells expressing a DA and exhibit lower levels of cytokine release relative to a DA x CD3 Binding Molecule comprising a rCD3-Binding Domain. The invention particularly concerns the use ofDA x CD3 Binding Moleculescomprising a vCD3-Binding Domain in the treatment of cancer and pathogen-associated diseases. The present invention is also directed to pharmaceutical compositions that comprise such molecule(s).本發明涉及包含vCD3-結合結構域的DA x CD3結合分子，所述vCD3-結合結構域包括CDRH1結構域、CDRH2結構域、CDRH3結構域、CDRL1結構域、CDRL2結構域和CDRL3結構域，其中至少一個在氨基酸序列上區別於rCD3-結合結構域的對應CDR的氨基酸序列，其中包含這種vCD3-結合結構域的DA x CD3結合分子相對於包含這種rCD3-結合結構域的DA x CD3結合分子展示對CD3改變的親和力。本發明具體涉及這種包含vCD3-結合結構域的DA x CD3結合分子，其相對於包含rCD3-結合結構域的DA x CD3結合分子展示對CD3降低的親和力，並且能夠介導表達DA的靶細胞的重定向殺傷並且展示較低水準的細胞因數釋放。本發明具體涉及包含vCD3-結合結構域的DA x CD3結合分子在治療癌症和病原體相關疾病中的用途。本發明也涉及包含這種分子（一種或多種）的藥物組合物。
