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 cancer comprising administering to a subject with cancer an antibody or antigen-binding antibody fragment that binds to a tumor-associated antigen (TAA), wherein the antibody or antigen-binding antibody fragment is conjugated to pro-2-pyrrolinodoxorubicin (P2PDox), wherein the antibody comprises human constant regions selected from the group consisting of IgG1, IgG2, IgG3 and IgG4.