AI Article Synopsis

  • - The study investigates the use of human serum albumin-based Drug-Free Macromolecular Therapeutics (DFMT) as a new treatment strategy for Chronic Lymphocytic Leukemia (CLL) by targeting CD20 and CD38 receptors on B cells without using conventional drugs.
  • - DFMT involves a two-step process to trigger apoptosis in malignant cells, utilizing bispecific engagers made from Fab' fragments of two antibodies and a multivalent effector molecule, showing promise in 56 patient samples.
  • - Results showed dual-targeting (both CD20 and CD38) was more effective than single-target approaches, with higher receptor expressions leading to better treatment outcomes and potential for personalized therapy, although further research is needed.

Article Abstract

This study explores the efficacy of human serum albumin (HSA)-based Drug-Free Macromolecular Therapeutics (DFMT) in treating Chronic Lymphocytic Leukemia (CLL), a prevalent adult leukemia subtype. DFMT, a novel strategy, employs biomimetic crosslinking of CD20 and CD38 receptors on malignant B cells without the need for low molecular weight drugs. Apoptosis is initiated via a two-step process: i) Recognition of a bispecific engager, Fab' fragment conjugated with morpholino oligonucleotide (Fab'-MORF1), by a cell surface antigen; followed by ii) crosslinking of the MORF1-decorated cells with a multivalent effector, HSA holding multiple copies of complementary MORF2, HSA-(MORF2)x. Herein we evaluated the efficacy of HSA-based DFMT in the treatment of 56 samples isolated from patients diagnosed with CLL. Fab' fragments from Obinutuzumab (OBN) and Isatuximab (ISA) were employed in the synthesis of anti-CD20 (Fab'-MORF1) and anti-CD38 (Fab'-MORF1) bispecific engagers. The efficacy of DFMT was significantly influenced by the expression levels of CD20 and CD38 receptors. Dual-targeting DFMT strategies (CD20 + CD38) were more effective than single-target approaches, particularly in samples with elevated receptor expression. Pretreatment of patient cells with gemcitabine or ricolinostat markedly increased cell surface CD20 and CD38 expression, respectively. Apoptosis was effectively initiated in 62.5% of CD20-targeted samples and in 42.9% of CD38-targeted samples. Our findings demonstrate DFMT's potential in personalized CLL therapy. Further research is needed to validate these outcomes in a larger number of patient samples and to explore DFMT's applicability to other malignancies.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13346-024-01629-3DOI Listing

Publication Analysis

Top Keywords

cd38 receptors
12
cd20 cd38
12
human serum
8
drug-free macromolecular
8
macromolecular therapeutics
8
chronic lymphocytic
8
lymphocytic leukemia
8
patient cells
8
crosslinking cd20
8
cell surface
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!