In some aspects, the invention relates to an antibody-drug conjugate, comprising an antibody; a linker; and at least two active agents. In preferred embodiments, the linker comprises a peptide sequence of a plurality of amino acids, and at least two of the active agents are covalently coupled to side chains of the amino acids. The antibody-drug conjugate may comprise a self-immolative group, preferably two-self-immolative groups. The linker may comprise an O-substituted oxime, e.g., wherein the oxygen atom of the oxime is substituted with a group that covalently links the oxime to the active agent; and the carbon atom of the oxime is substituted with a group that covalently links the oxime to the antibody.
在某些方面,本发明涉及一种
抗体-药物共轭物,包括
抗体、连接体和至少两种活性剂。在优选的实施方案中,连接体包括由多个
氨基酸组成的肽序列,至少两种活性剂与
氨基酸侧链共价偶联。
抗体-药物共轭物可包括一个自巯基,最好是两个自巯基。连接体可包括 O-取代的
肟,例如,其中
肟的氧原子被一个能将
肟与活性剂共价连接的基团取代;
肟的碳原子被一个能将
肟与
抗体共价连接的基团取代。