Next Article in Journal / Special Issue
Dissecting the Entry Route of Saporin-based a-CD7 Immunotoxins in Human T-Cell Acute Lymphoblastic Leukaemia Cells
Previous Article in Journal / Special Issue
Species-Dependent Functionality of the Human Cytolytic Fusion Proteins Granzyme B-H22(scFv) and H22(scFv)-Angiogenin in Macrophages
Article Menu

Export Article

Open AccessReview
Antibodies 2013, 2(1), 19-49; doi:10.3390/antib2010019

Improving the Therapeutic Potential of Human Granzyme B for Targeted Cancer Therapy

1
Pharmedartis GmbH, Aachen 52074, Germany
2
Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, University Hospital RWTH Aachen, Aachen 52074, Germany
3
Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen 52074, Germany
These author contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 13 December 2012 / Revised: 4 January 2013 / Accepted: 8 January 2013 / Published: 16 January 2013
(This article belongs to the Special Issue Recombinant Immunotoxins)
View Full-Text   |   Download PDF [359 KB, uploaded 16 January 2013]   |  

Abstract

Conventional cancer treatments lack specificity and often cause severe side effects. Targeted therapeutic approaches are therefore preferred, including the use of immunotoxins (ITs) that comprise cell-binding and cell death-inducing components to allow the direct and specific delivery of pro-apoptotic agents into malignant cells. The first generation of ITs consisted of toxins derived from bacteria or plants, making them immunogenic in humans. The recent development of human cytolytic fusion proteins (hCFP) consisting of human effector enzymes offers the prospect of highly-effective targeted therapies with minimal side effects. One of the most promising candidates is granzyme B (GrB) and this enzyme has already demonstrated its potential for targeted cancer therapy. However, the clinical application of GrB may be limited because it is inactivated by the overexpression in tumors of its specific inhibitor serpin B9 (PI-9). It is also highly charged, which means it can bind non-specifically to the surface of non-target cells. Furthermore, human enzymes generally lack an endogenous translocation domain, thus the endosomal release of GrB following receptor-mediated endocytosis can be inefficient. In this review we provide a detailed overview of these challenges and introduce promising solutions to increase the cytotoxic potency of GrB for clinical applications. View Full-Text
Keywords: immunotherapy; immunotoxin; human cytolytic fusion protein; bio-engineering; serpin B9; surface-charge; endosomal release immunotherapy; immunotoxin; human cytolytic fusion protein; bio-engineering; serpin B9; surface-charge; endosomal release
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Hehmann-Titt, G.; Schiffer, S.; Berges, N.; Melmer, G.; Barth, S. Improving the Therapeutic Potential of Human Granzyme B for Targeted Cancer Therapy. Antibodies 2013, 2, 19-49.

Show more citation formats Show less citations formats

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