BARTH, Prof Dr Dr Stefan - Position presently held
Full Professor of Cancer Biotechnology

Research interests
Knowledge-driven development of disease-specific diagnostic and therapeutic fusion proteins

Main areas of research/expertise
Medical biotechnology, antibody technologies, protein engineering, immunodiagnostics, bioassay development & integration, immunotherapeutics, targeted human cytolytic fusion proteins, SNAP-tag based fusion proteins, ex vivo / in vivo targeting

Biosketch
Full Professor of Cancer Biotechnology in the Department of Integrated Biomedical Sciences at University of Cape Town and full member at the Institute for Infectious Disease and Molecular Medicine IDM (since 2015). Executive Director of the UCT accredited Medical Biotechnology & Immunotherapy (MB&I) Research Unit. Previous Tier 1 South African Research Chair in Cancer Biotechnology hosted by the Institute of Infectious Disease and Molecular Medicine (IDM) and the Department of Integrated Biomedical Sciences, awarded by the South African Research Chairs Initiative (SARChI) of the Department of Science and Technology (DST), administered through the National Research Foundation (NRF) (until March 2025). University Professor for Experimental Medicine and Immunotherapy at the Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Germany (2006-2015). Head of Department of Pharmaceutical Product Development at the Fraunhofer Institute for Molecular Biology and Applied Ecology IME in Aachen, Germany (2000-2015). Habilitation in Experimental Internal Medicine (2001), DMSc in Experimental Medicine (Dr. rer. medic.) at the Department of Internal Medicine, University of Cologne, Germany (1997), PhD in biology (Dr. rer. nat.) at the Institute of Molecular Physiology and Biotechnology of Plants, University of Bonn, Germany (1994), MSc in Biology at the University of Bonn, Germany (1991).

Prof. Barth is co-founder of CURIT Biotech SA (PTY) Ltd; was co-founder of Pharmedartis GmbH (HRB 13916) and TOXAVIS GmbH (HRB 61471; financing POCDIA GmbH (HRB 9178) and TOXAVIS Pharmaceuticals GmbH (HRB 62750)), start-up companies in the areas of biotechnology and medical technologies. He is/was member in different scientific societies including e.g. German Society for Haematology and Oncology, German Cancer Society, European Association for Cancer Research and the British Society of Immunology. He has acted as reviewer for different funding societies including German Research Foundation (DFG), Alexander von Humboldt-Foundation, Wilhelm Sander Foundation, Bavarian Research Foundation, Swiss National Science Foundation, Austrian Science Fund, Dutch Cancer Society, Worldwide Cancer Research. He also served as reviewer for different scientific journals including Cancer Letters, Biological Chemistry, Bioconjugate Chemistry, Molecular Cancer Therapeutics, Haematologica, Journal of Controlled Release, International Journal of Cancer, PLOS ONE, Cancer Research, Clinical Cancer Research, Molecular Oncology, Apoptosis, mAbs, Biomaterials, Theranostics, and Nature Methods. He received a Tier 1 South African Research Chair in Cancer Biotechnology, 1st prize in Boehringer Ingelheims InnoCentive Challenge for novel treatment approaches to stop the allergic march towards asthma, eight 1st poster prizes at international conferences and three 1st funding prizes for the business concept of Pharmedartis. He is continuously invited to international conferences and workshops in scientific areas including medical biotechnology, immunotherapy, and others.

Prof. Barth started his work in medical biotechnology in 1994 and during the last >25 years of work he successfully applied for about 60 funded projects in Germany, 14 in South Africa, and 1 in Brazil, thus raised R452,638,857 (21,889,000 € (R386.938.761) in Germany and R65,700,096 in South Africa), filed 37 different patent family applications (the first 25 are granted – mainly US & EU) in total ~180 individual patent applications, wrote 221 peer-reviewed publications (ORCHID) with a cumulative total IF of ~1,100 (h-Index: 46, i10.index: 166) with >460.000 views from journal homepages, >51.000 reads in Research Gate (RG RI Score: 2,349), and >7.000 citations in Google Scholar, and supervised 246 students. About 30 % of these former students are working in academia, 60 % in industry including Afrigen Biologics, Bayer, Cape Biologix, Biovac, Covagen, Ganymed, Grünenthal, Janssen, Limmatech, Miltenyi, Morphosys, Rakuten Medical, Roche, Sanofi-Aventis, Takeda Oconolgy Watchmaker Genomics including e.g. Sales and Marketing Director of Milenyi Biotech, Project Leader Mass Spectrometry at Evotec, Senior Director Corporate Portfolio Management at Grünenthal, Senior Scientist at F-star Biotechnology, Director External Innovation at Covagen, Patent Lawyer at König Szyka Tilman von Renesse, Senior Director, Business Development & Licensing at Bayer Healthcare, to specify a few.

During the first eight years since establishing a laboratory at IDM in July 2016, I directly supervised a total of 107 students (14 PostDocs, 23 PhD, 21 MSc, 49 Hons/Interns) and graduated 15 Hons students, 10 MSc students, 2 MSc upgraded to PhD, and 9 PhD students. In 2024, 7 PhD and 5 MSc students are expected to submit their theses. Most of the students were also co-supervised by postdoctoral fellows including Dr. Shivan Chetty, Dr. Krupa Naran, Dr. Eden Padayachee, Dr. Dharanidharan Ramamurthy and Dr. Olusiji Alex Akinrinmade. With my SARChI Chair I provided grant holder linked bursaries to students (range between 8-16 per year) including black (range between 88 and 100%) and female (at 55% and mostly higher). Through additional funding, a range of additional students was supported through MB&I (range between 16 and 29) including black (with a steadily increasing number of black students starting from 75% in 2016 to 93% in 2022) and female (mostly well above 55%).

Research
The major aim of our research is the use of medical biotechnology methods including antibody technologies, protein engineering & expression, to develop and evaluate knowledge-based innovative recombinant immunodiagnostics and therapeutics. The main characteristics of these novel agents are: a) disease-specific activities, b) reduced unspecific side effects, and c) reduced immunogenicity.

Prof. Barth started his work on recombinant immunotoxins (rITs) composed of a targeting antibody fragment recombinantly fused to Pseudomonas exotoxin A (ETA). After establishing bacterial periplasmic expression by inducing an osmotic stress response in the presence of compatible solutes, this method was used for successful expression of rITs including, amongst others the worldwide first CD30-targeting immunotoxin [8, 9] as well as targeted completely human cytolytic fusion proteins (hCFP) by replacing ETA with human apoptosis inducing enzymes [5]. In 2000 Prof. Barth was hired at Fraunhofer IME as head of Department for Pharmaceutical Product Development and was appointed in parallel as Professor for Experimental Medicine and Immunotherapy at the University Hospital Aachen (RWTH). Using the same principles of the protein engineering work he invented single stranded cell surface receptor targeting aptamers for targeted delivery of controlled numbers of siRNAs inducing cell death [P1]. In 2015 Prof. Barth got awarded for the Tier 1 South African Research Chair in Cancer Biotechnology, moved to South Africa and establish the Medical Biotechnology & Immunotherapy Research Unit at the Institute of Infectious Disease and Molecular Medicine allowing to transfer all established technologies and focus on next generation constructs with reduced immunogenicity: in consequence, Prof. Barth was the worldwide first to describe B-cell receptor [7] or proprietary CD64 and CD89 targeting immunotoxins or hCFP based on a human serpin-B9 insensitive Granzyme B. Second unique selling point relates to SNAP tag-based antibody fusion proteins [1] used for imaging [6] or therapeutic purposes [4, 3, 2]. Additional best output includes granted Patents covering recombinant anti-CD64 immunotoxins, human angiogenin, granzyme B, granzyme M, MAP tau based hCFP, SNAP tag-based antibody fusion proteins for targeted photodynamic therapy, as well as targets overexpressed on the surface of cancer cells.
For references see selected publications

Collaborations

UCT
Name	Affiliation	Project area
Prof Dirk Lang	Anatomy	Confocal imaging
Prof Sharon Prince	Human Biology	CDCTA
Prof Virna Leaner	IBMS	CDCTA
Dr Brandon Weber	CeBER	Process development
Prof Roger Hunter	Chemistry	CDCTA / Novel chemical conjugates
Prof Darren Martin	Computational Biology	AI driven identification of CSR
Prof Komala Pillay	Pathology	Historical FFPE tissue sections
Prof Thomas Scriba	SATVI	TB diagnosis
Prof Dirk Lang	HUB	Confocal microscopy
National
Name	Affiliation	Project area
Prof Bert Klumperman	University of Stellenbosch	BG modified chemical substances
Belinda Shaw	Cape Bio Pharms / Cape Biologix	Plant expression platform
International
Name	Affiliation	Project area
Prof Paolo Carloni	Forschungszentrum Jülich	Supercomputing Simulation
Dr Wolfgang Richter	Tube Pharmaceuticals	Novel Chemical Conjugates
Dr Klaus Pors	University of Bradford	Chemical conjugates
Prof Bernd Pilcher	University of Tübingen	Radioimaging
Prof Anna Blakney	University of British Columbia	Targeted RNA delivery
Prof Huining He	Tianjin Medical University	SNAP tag antibodies for siRNA delivery

People

Group members	Position
Nkhasi Lekena	JRF
Roshan Ebrahim	Senior Scientific Officer
Gael Siwe	Postdoctoral Fellow
Liyabona Mpondo	PhD Student
Marc Henry	PhD Student
Masala Mugeri	PhD Student
Zaria Malindi	PhD Student
Salizwa Malindi	PhD Student
Emmanuel Fajemisin	PhD Student
Siphelele Sanele Cingo	PhD Student
Amanda Shangase	PhD Student
Nosipho Msimango	MSc Student
Thabo Matshoba	MSc/PhD Student
Emma Jakubicka	Intern from MIT
Samantha Levetan	Honours

Selected Publications

1. Hussain A.F., et al. – One step site-specific antibody fragment conjugation using SNAP tag technology. Nature Protocols 14: 3101-3125 (2019), doi: 10.1038/s41596-019-0214-y.
IF 13.491. Principal investigator, conceptualised idea for research, supervisor of lead author, main inventor, project leader/budget owner. Protocols describing the generation and use of SNAP antibody fusions. 

2. Dhandapani R., et al. – Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB positive sensory neurons. Nature Commun 9(1): 1640 (2018), PMID: 29691410, doi: 10.1038/s41467-018-04049-3.
IF 14.92. Conceptualised idea for research, co-developed research, editorial input. First worldwide preclinical in vivo study confirming a TrkB-specific ligand fused to SNAP and conjugated to a near infrared photosensitizer to reduce neuropathic pain. 

 3. Amoury M., et al. - A novel approach for targeted elimination of CSPG4-positive triple negative breast cancer using a MAP-tau based fusion protein. Int J Cancer 139(4): 916-24 (2016). PMID: 27037627, doi: 10.1002/ijc.30119.
IF 7.396. Principal investigator, conceptualised idea for research, supervisor of lead author, main inventor, project leader/budget owner. Preclinical in vivo study confirming the cytotoxic activity of a CSPG4-specific hCFP. 

 4. Woitok M., et al. – The efficient elimination of solid tumor cells by EGFR- and Her2-specific scFv-SNAP fusion proteins conjugated to benzylguanine-modified auristatin F. Cancer Letters 381(2): 323-30 (2016). PMID: 27502168, doi: 10.1016/j.canlet.2016.08.003.
IF 8.679. *shared principal investigator, conceptualised idea for research, supervisor of lead author, main inventor, project leader/budget owner. First worldwide in vitro study confirming cytotoxic activity of a SNAP antibody fusion conjugated to Auristatin F. 

 5. Schiffer S., et al. - Efficacy of an adapted Granzyme B-based anti-CD30 cytolytic fusion protein against PI-9-positive classical Hodgkin lymphoma cells in a murine model. Blood Cancer Journal 3: e106 (2013), PMID: 23524591, doi: 10.1038/bcj.2013.4.
IF 11.037. Principal investigator, conceptualised idea for research, supervisor of lead author, main inventor, project leader/budget owner. First worldwide preclinical in vivo study confirming the cytotoxic activity of a CD30-targeting serpin B9 resistant human granzyme B on NK-attack-resistant tumors. 

 6. Kampmeier F., et al. – Rapid optical imaging of EGF-receptor expression with a single chain antibody SNAP-tag fusion protein. European Journal of Nuclear Medicine and Molecular Imaging 37(19): 1926-1934 (2010), PMID: 20449589, doi: 10.1007/s00259-010-1482-5.
IF 9.236. Principal investigator, conceptualised idea for research, supervisor of lead author, main inventor, project leader/budget owner. Major preclinical scientific study confirming the use of near infrared fluorophore conjugated SNAP antibody fusions for preclinical in vivo optical imaging. 

7. Stöcker M., et al. - Antigen-specific targeting and elimination of EBV-transformed B-cells by allergen-toxins. Journal of Allergy and Clin Immunol 116(4):910-915 (2005), PMID: 16210069, doi: 10.1016/j.jaci.2005.07.022. IF 10.79. Principal investigator, conceptualised idea for research, supervisor of lead author, main inventor, project leader/budget owner. First world-wide preclinical study confirming the selective killing of allergen reactive B lymphocytes with a major pollen allergen targeting rIT. 

8. Tur M.K., et al.- Recombinant CD64-specific single chain Immunotoxin exhibits specific cytotoxicity against acute myeloid leukemia cells. Cancer Res 63 (23):8414-8419 (2003), PMID: 14679004, doi: Published December 2003.
IF 12.7. Principal investigator, conceptualised idea for research, supervisor of lead author, main inventor, project leader/budget owner. First worldwide in vitro study confirming dose dependent cytotoxicity of an anti-CD64 rIT. Basis for a series of patent applications. 

9. Barth S., et al. - Ki-4(scFv)-ETA’, a new recombinant anti-CD30 immunotoxin with highly specific cytotoxic activity against disseminated Hodgkin tumors in SCID mice. Blood 95 (12):3909-3914 (2000), PMID: 10845927, doi: 10.1182/blood.V95.12.3909.
IF 22.11. Wrote the manuscript, conceptualised idea for research, co-developed research, project leader/budget owner. First world-wide preclinical in vivo study confirming selective elimination of tumor xenografts. 

 PATENT 

P1. Barth S., et al. - Immuno-RNA-Constructs. European Patent EP1976564 (2006), Chinese Patent 101340934 (2013), United States Patent US8829178 (2014), Canadian Patent CA2633776 (2018)
Patent family protecting multivalent eukaryotic elongation factor targeting siRNA delivering aptamer/antibody constructs.

Please find complete list of publications at Google Scholar