Evaluating the influence of common antibiotics on the efficacy of a recombinant immunotoxin in tissue culture.

Abstract

OBJECTIVE:

Recombinant immunotoxins (RITs) are antibody-toxin fusion proteins that can selectively eliminate populations of cells expressing specific surface receptors. They are in evaluation as therapeutic agents for cancer. RITs based on Pseudomonas exotoxin A (PE) are in use clinically for the treatment of hairy cell leukemia, and under trial for the treatment of other cancers. In an effort to improve the efficacy of PE-based RITs, we evaluated the potential of combination therapy with several common antibiotics (tetracycline, chloramphenicol, streptomycin, linezolid, fusidic acid, and kanamycin) on human cell lines HEK293, OVCAR8, and CA46. Antibiotics were selected based on their potential to inhibit mitochondrial protein synthesis and disrupt energy metabolism in cancer cells.

RESULTS:

Tetracycline, chloramphenicol, linezolid, and fusidic acid alone killed cultured human cells at high concentrations. At high but nontoxic concentrations of each antibiotic, only chloramphenicol treatment of the Burkitt's lymphoma cell line CA46 showed enhanced cytotoxicity when paired with an anti-transferrin receptor/PE RIT. This result, however, could not be replicated in additional Burkitt's lymphoma cell lines Ramos and Raji. Although the six antibiotics we tested are not promising candidates for RIT combination therapy, we suggest that fusidic acid could be considered independently as a potential cancer therapeutic.

• Authors: Yuyi Zhu, John E Weldon
• Journal: BMC research notes (BMC Res Notes) Vol. 12 Issue 1 Pg. 293 (May 27 2019) ISSN: 1756-0500 [Electronic] England
• PMID: 31133049 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Antibodies, Monoclonal
• Bacterial Toxins
• Exotoxins
• Immunotoxins
• Mitochondrial Proteins
• Recombinant Fusion Proteins
• Virulence Factors
• Kanamycin
• Fusidic Acid
• Chloramphenicol
• ADP Ribose Transferases
• Pseudomonas aeruginosa exotoxin A
• Tetracycline
• Linezolid
• Streptomycin

Topics

• ADP Ribose Transferases (pharmacology)
• Anti-Bacterial Agents (pharmacology)
• Antibodies, Monoclonal (chemistry, pharmacology)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Bacterial Toxins (pharmacology)
• Cell Line, Tumor
• Chloramphenicol (pharmacology)
• Epithelial Cells (drug effects, metabolism, pathology)
• Exotoxins (pharmacology)
• Fusidic Acid (pharmacology)
• HEK293 Cells
• Humans
• Immunotoxins (pharmacology)
• Inhibitory Concentration 50
• Kanamycin (pharmacology)
• Linezolid (pharmacology)
• Lymphocytes (drug effects, pathology)
• Mitochondria (drug effects, metabolism)
• Mitochondrial Proteins (antagonists & inhibitors, biosynthesis)
• Recombinant Fusion Proteins (pharmacology)
• Streptomycin (pharmacology)
• Tetracycline
• Virulence Factors (pharmacology)