Biochemical and cellular investigations on the potential use of affibodies in leukemia therapy

Biochemical and cellular investigations on the potential use of affibodies in leukemia therapy 2022 - 2023
Acronym: LEUKEMIA. Grant no.779/14.06.2022
Project director: Stefan Szedlacsek
Fulbright Visiting Scholar Program/ FFC_3-0119.
External website: full link

Affibody molecules are highly promising therapeutic candidates due to their advantageous features like: small size, efficient delivery, straightforward engineering towards improved formats, site-directed conjugation of payloads, possibility of GMP production by chemical synthesis or inexpensive bacterial production leading to low product costs.

The initial phase of this project originated from the conceptual framework developed during the Fulbright Visiting Scholar stage at the MD Anderson Cancer Center (Houston, USA), where the foundation was laid for the rational design of affibody, drug conjugates as potential targeted therapies for leukemia.

Building upon this foundation, the project now aims to investigate the therapeutic potential of these affibody–drug conjugates and advance them as close as possible to the validation of a new class of drugs for certain forms of leukemia.

In its current stage, the project continues and expands the scientific directions initiated abroad, integrating biochemical, molecular, and cellular approaches. The long-term objective is to consolidate in Romania a critical mass of researchers and PhD students capable of conducting advanced molecular research in leukemia, in close collaboration with scientists from the MD Anderson Cancer Center and other international partners.

Stefan Szedlacsek, Dr.
Stefan Szedlacsek, Dr.

Head of Department

Prof. Dr. Stefan Szedlacsek is the Head of the Enzymology Department at the Institute of Biochemistry of the Romanian Academy. He holds a PhD degree in Biotechnology from Polytechnical University of Bucharest as well as a MSc in Organic Synthesis (Polytechnical University, Bucharest) and MSc in Mathematics (University of Bucharest). As a visiting scientist, he performed research in the field of cholesterol metabolism at the University of Illinois at Urbana-Champaign (USA), where he succeeded to evidence a new pathway in the metabolism of oxysterols.  He is an “Alexander von Humboldt” fellow and worked in Germany, in the Institute of Biochem More...

Adina-Gabriela Puiu, PhD Student
Adina-Gabriela Puiu, PhD Student

Research Assistant

Adina has a Bachelor's degree in Biology and a Master's degree in Applied Genetics and Biotechnology from the Faculty of Biology, University of Bucharest. She is a PhD student and Research Assistant at the Institute of Bio More...

Andrei-Mihai Vasilescu, PhD Student
Andrei-Mihai Vasilescu, PhD Student

Research Assistant

Andrei-Mihai Vasilescu is a researcher in the Institute of Biochemistry of the Romanian Academy. Andrei-Mihai is currently working in Enzymology in the Enzymology.

The specific objectives are the following:

1) Biochemical characterization of AfDC

2) Evaluation of the efficiency of 3-5 affibody-drug conjugates on leukemic cell lines

3) In vivo assessment of affibody-drug conjugates efficiency on transgenic models of human leukemias

Recently, results derived from these objectives – including the design of a DNA minicircle for STAT3 inhibition in ovarian cancer and the development of a novel anti-B7-H3 affibody–drug conjugate for leukemia – have been published in Frontiers in Pharmacology (2025), highlighting the scientific continuity and translational relevance of the project.

Building upon the original concepts developed by Prof. Szedlacsek during his Fulbright research at the MD Anderson Cancer Center, the project achieved two major experimental directions that validated and extended those initial ideas.

First, a new class of recombinant affibody–drug conjugates was designed and biochemically characterized, demonstrating selective cytotoxicity against leukemic cells expressing specific surface biomarkers. These molecules proved capable of inducing apoptosis and inhibiting cell proliferation in vitro, providing strong evidence for their therapeutic potential in hematological malignancies.

In parallel, a synthetic DNA minicircle inhibitor was developed to block STAT3 activation, a key signaling pathway involved in tumor progression and resistance. This approach successfully reduced cancer cell viability, induced apoptosis, and downregulated STAT3-dependent anti-apoptotic genes, confirming the feasibility of nucleic acid–based molecular therapies derived from the project’s core principles.

 

Together, these results consolidate the conceptual framework initiated under the Fulbright program and demonstrate the capacity to translate innovative biochemical strategies into functional therapeutic models.

Clarkson  

Published papers

1) Andrei-Mihai Vasilescu, Adina-Gabriela Vasilescu, Livia Elena Sima, Cristian V.A. Munteanu, Natalia Baran, Stefan-Eugen Szedlacsek; "A novel cytotoxic anti-B7-H3 affibody with therapeutic potential in acute myeloid leukemia"Frontiers in Pharmacology (Article number 1684226): 1-13, (2025) DOI: 10.3389/fphar.2025.1684226IF: 4.8.

2) Adina-Gabriela Vasilescu, Andrei-Mihai Vasilescu, Livia Elena Sima, Natalia Baran, Ștefan-Eugen Szedlacsek; "Breaking the cancer code: a novel DNA minicircle to disable STAT3 in ovarian cancer cells SKOV3"Frontiers in Pharmacology (Article number: 1673427): 1-15, (2025); DOI: 10.3389/fphar.2025.1673427; IF: 4.80.