Immunoconjugates with an Intracellularly-Cleavable Linkage

摘要

The present invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a therapeutic moiety, and further relates to processes for making and using the conjugates.

主权项

1. A method for treating autoimmune disease, comprising administering to a subject with an autoimmune disease a conjugate having a structural formula selected from the group consisting of MAb-CL2A-SN-38, MAb-CL6-SN-38, MAb-CL7-SN-38, MAb-CLX-SN-38 and MAb-CLY-SN-38, with a structure represented by: where R is hydrogen or C1 to C10 alkyl group and AA is selected from any one of the following L-amino acids: alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine, where R and R′ can be independently hydrogen or methyl; and when R=R′=methyl, referred to as MAb-CL2E-SN-38, wherein said MAb binds to an antigen selected from the group consisting of TNF-α, IL-2R, CD3, CD4, CD19, CD20, CD22, CD25, CD40L, CD52, HLA-DR and macrophage migration-inhibitory factor (MIF).