AUTHOR=Theyab Abdulrahman , Alsharif Khalaf F. , Alzahrani Khalid J. , Oyouni Atif Abdulwahab A. , Hawsawi Yousef MohammedRabaa , Algahtani Mohammad , Alghamdi Saad , Alshammary Amal F. TITLE=New insight into strategies used to develop long-acting G-CSF biologics for neutropenia therapy JOURNAL=Frontiers in Oncology VOLUME=12 YEAR=2023 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1026377 DOI=10.3389/fonc.2022.1026377 ISSN=2234-943X ABSTRACT=

Over the last 20 years, granulocyte colony-stimulating factors (G-CSFs) have become the major therapeutic option for the treatment of patients with neutropenia. Most of the current G-CSFs require daily injections, which are inconvenient and expensive for patients. Increased understanding of G-CSFs’ structure, expression, and mechanism of clearance has been very instrumental in the development of new generations of long-acting G-CSFs with improved efficacy. Several approaches to reducing G-CSF clearance via conjugation techniques have been investigated. PEGylation, glycosylation, polysialylation, or conjugation with immunoglobulins or albumins have successfully increased G-CSFs’ half-lives. Pegfilgrastim (Neulasta) has been successfully approved and marketed for the treatment of patients with neutropenia. The rapidly expanding market for G-CSFs has increased demand for G-CSF biosimilars. Therefore, the importance of this review is to highlight the principle, elimination’s route, half-life, clearance, safety, benefits, and limitations of different strategies and techniques used to increase the half-life of biotherapeutic G-CSFs. Understanding these strategies will allow for a new treatment with more competitive manufacturing and lower unit costs compared with that of Neulasta.