Oncotarget

Reviews:

Advances in epidermal growth factor receptor specific immunotherapy: lessons to be learned from armed antibodies

Fleury Augustin Nsole Biteghe, Neelakshi Mungra, Nyangone Ekome Toung Chalomie, Jean De La Croix Ndong, Jean Engohang-Ndong, Guillaume Vignaux, Eden Padayachee, Krupa Naran and Stefan Barth _

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Oncotarget. 2020; 11:3531-3557. https://doi.org/10.18632/oncotarget.27730

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Abstract

Fleury Augustin Nsole Biteghe1,*, Neelakshi Mungra2,*, Nyangone Ekome Toung Chalomie4, Jean De La Croix Ndong5, Jean Engohang-Ndong6, Guillaume Vignaux7, Eden Padayachee8, Krupa Naran2,* and Stefan Barth2,3,*

1 Department of Radiation Oncology and Biomedical Sciences, Cedars-Sinai Medical, Los Angeles, CA, USA

2 Medical Biotechnology & Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

3 South African Research Chair in Cancer Biotechnology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

4 Sun Yat-Sen University, Zhongshan Medical School, Guangzhou, China

5 Department of Orthopedic Surgery, New York University School of Medicine, New York, NY, USA

6 Department of Biological Sciences, Kent State University at Tuscarawas, New Philadelphia, OH, USA

7 Arctic Slope Regional Corporation Federal, Beltsville, MD, USA

8 Department of Physiology, University of Kentucky, Lexington, KY, USA

* These authors contributed equally to this work

Correspondence to:

Stefan Barth,email: stefan.barth@uct.ac.za

Keywords: epidermal growth factor receptor (EGFR); recombinant immunotoxins (ITs); targeted human cytolytic fusion proteins (hCFPs); recombinant antibody-drug conjugates (rADCs); recombinant antibody photoimmunoconjugates (rAPCs)

Received: May 30, 2020     Accepted: August 11, 2020     Published: September 22, 2020

ABSTRACT

The epidermal growth factor receptor (EGFR) has been recognized as an important therapeutic target in oncology. It is commonly overexpressed in a variety of solid tumors and is critically involved in cell survival, proliferation, metastasis, and angiogenesis. This multi-dimensional role of EGFR in the progression and aggressiveness of cancer, has evolved from conventional to more targeted therapeutic approaches. With the advent of hybridoma technology and phage display techniques, the first anti-EGFR monoclonal antibodies (mAbs) (Cetuximab and Panitumumab) were developed. Due to major limitations including host immune reactions and poor tumor penetration, these antibodies were modified and used as guiding mechanisms for the specific delivery of readily available chemotherapeutic agents or plants/bacterial toxins, giving rise to antibody-drug conjugates (ADCs) and immunotoxins (ITs), respectively. Continued refinement of ITs led to deimmunization strategies based on depletion of B and T-cell epitopes or substitution of non-human toxins leading to a growing repertoire of human enzymes capable of inducing cell death. Similarly, the modification of classical ADCs has resulted in the first, fully recombinant versions. In this review, we discuss significant advancements in EGFR-targeting immunoconjugates, including ITs and recombinant photoactivable ADCs, which serve as a blueprint for further developments in the evolving domain of cancer immunotherapy.


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