Pro-drug form (P2PDox) of the highly potent 2-pyrrolinodoxorubicin conjugated to antibodies for targeted therapy of cancer

摘要

Disclosed are methods, compositions and uses of conjugates of prodrug forms of 2-pyrrolinodoxorubicin (P2PDox) with antibodies or antigen-binding fragments thereof (ADCs), with targetable construct peptides or with other targeting molecules that are capable of delivering the P2PDox to a targeted cell, tissue or pathogen. Once delivered to the target cell, the ADC or peptide conjugate is internalized, a highly toxic 2-pyrrolinodoxorubicin (2-PDox) is released intracellularly. The P2PDox-peptide or ADC conjugates are of use to treat a wide variety of diseases, such as cancer, autoimmune disease or infectious disease.

主权项

1. A method of treating an autoimmune disease, comprising administering to a subject with an autoimmune disease a conjugate comprising (i) pro-2-pyrrolinodoxorubicin (P2PDox) wherein P2PDox is N-(4,4-diacetoxybutyl)doxorubicin; and (ii) an antibody or antigen-binding antibody fragment attached to the P2PDox, wherein the an antibody or antigen-binding antibody fragment binds to a B-cell antigen.