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Bispecific Antibody Therapy for Effective Cardiac Repair through Redirection of Endogenous Stem Cells
Author(s) -
Huang Ke,
Li Zhenhua,
Su Teng,
Shen Deliang,
Hu Shiqi,
Cheng Ke
Publication year - 2019
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.201900009
Subject(s) - stem cell , medicine , cd34 , cardiac function curve , cell therapy , monoclonal antibody , cancer research , transplantation , immunotherapy , in vivo , immune system , antibody , immunology , heart failure , cardiology , microbiology and biotechnology , biology
Bone marrow stem cells (BMSCs) are a promising strategy for cardiac regenerative therapy for myocardial infarction (MI). However, cell transplantation has to overcome a number of hurdles, such as cell quality control, clinical practicality, low cell retention/engraftment, and immune reactions when allogeneic cells are used. Bispecific antibodies (BsAbs) have been developed as potential agents in cancer immunotherapy but their application is sparse in cardiovascular diseases. In the present study, BsAbs are designed by chemical cycloaddition of F(ab′) 2 fragments from monoclonal anti‐CD34 and anti‐ cardiac myosin heavy chain (CMHC) antibodies, which specifically targets circulating CD34‐positive cells and injured cardiomyocytes simultaneously. It is hypothesized that intravenous administration of stem cell re‐directing (SCRD) BsAbs (anti‐CD34‐F(ab′) 2 –anti‐CMHC‐F(ab′) 2 ) can home endogenous BMSCs to the injured heart for cardiac repair. The in vivo studies in a mouse model with heart ischemia/reperfusion (I/R) injury demonstrate the safety and therapeutic potency of SCRD BsAb, which supports cardiac recovery by reducing scarring, promoting angiomyogenesis, and boosting cardiac function.