Next Article in Journal
Structural Changes in Stx1 Engineering Monoclonal Antibody Improves Its Functionality as Diagnostic Tool for a Rapid Latex Agglutination Test
Previous Article in Journal
Acknowledgement to Reviewers of Antibodies in 2017
Previous Article in Special Issue
Enzyme-Based Labeling Strategies for Antibody–Drug Conjugates and Antibody Mimetics
Article Menu

Export Article

Open AccessReview
Antibodies 2018, 7(1), 8; https://doi.org/10.3390/antib7010008

Therapeutic Antibody-Like Immunoconjugates against Tissue Factor with the Potential to Treat Angiogenesis-Dependent as Well as Macrophage-Associated Human Diseases

Department of Surgery Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University College of Medicine, Columbus, OH 43210, USA
Received: 10 October 2017 / Revised: 10 January 2018 / Accepted: 18 January 2018 / Published: 23 January 2018
(This article belongs to the Special Issue Therapeutic Antibodies)
View Full-Text   |   Download PDF [1677 KB, uploaded 25 January 2018]   |  

Abstract

Accumulating evidence suggests that tissue factor (TF) is selectively expressed in pathological angiogenesis-dependent as well as macrophage-associated human diseases. Pathological angiogenesis, the formation of neovasculature, is involved in many clinically significant human diseases, notably cancer, age-related macular degeneration (AMD), endometriosis and rheumatoid arthritis (RA). Macrophage is involved in the progression of a variety of human diseases, such as atherosclerosis and viral infections (human immunodeficiency virus, HIV and Ebola). It is well documented that TF is selectively expressed on angiogenic vascular endothelial cells (VECs) in these pathological angiogenesis-dependent human diseases and on disease-associated macrophages. Under physiology condition, TF is not expressed by quiescent VECs and monocytes but is solely restricted on some cells (such as pericytes) that are located outside of blood circulation and the inner layer of blood vessel walls. Here, we summarize TF expression on angiogenic VECs, macrophages and other diseased cell types in these human diseases. In cancer, for example, the cancer cells also overexpress TF in solid cancers and leukemia. Moreover, our group recently reported that TF is also expressed by cancer-initiating stem cells (CSCs) and can serve as a novel oncotarget for eradication of CSCs without drug resistance. Furthermore, we review and discuss two generations of TF-targeting therapeutic antibody-like immunoconjugates (ICON and L-ICON1) and antibody-drug conjugates that are currently being tested in preclinical and clinical studies for the treatment of some of these human diseases. If efficacy and safety are proven in current and future clinical trials, TF-targeting immunoconjugates may provide novel therapeutic approaches with potential to broadly impact the treatment regimen of these significant angiogenesis-dependent, as well as macrophage-associated, human diseases. View Full-Text
Keywords: tissue factor; factor VII; antibodies; antibody-like immunoconjugates (ICON and L-ICON1); solid cancer; Leukemia; age-related macular degeneration; endometriosis; rheumatoid arthritis; atherosclerosis; angiogenesis; vascular endothelial cell; cancer cell; cancer stem cell; macrophage; fibroblast; B cell tissue factor; factor VII; antibodies; antibody-like immunoconjugates (ICON and L-ICON1); solid cancer; Leukemia; age-related macular degeneration; endometriosis; rheumatoid arthritis; atherosclerosis; angiogenesis; vascular endothelial cell; cancer cell; cancer stem cell; macrophage; fibroblast; B cell
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Hu, Z. Therapeutic Antibody-Like Immunoconjugates against Tissue Factor with the Potential to Treat Angiogenesis-Dependent as Well as Macrophage-Associated Human Diseases. Antibodies 2018, 7, 8.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Antibodies EISSN 2073-4468 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top