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 fo...
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | BMC Research Notes |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13104-019-4337-6 |
| _version_ | 1818302000989732864 |
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| author | Yuyi Zhu John E. Weldon |
| author_facet | Yuyi Zhu John E. Weldon |
| author_sort | Yuyi Zhu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T05:31:57Z |
| format | Article |
| id | doaj.art-c7ffdf43195946d8971733868a94b50c |
| institution | Directory Open Access Journal |
| issn | 1756-0500 |
| language | English |
| last_indexed | 2024-12-13T05:31:57Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Research Notes |
| spelling | doaj.art-c7ffdf43195946d8971733868a94b50c2022-12-21T23:58:03ZengBMCBMC Research Notes1756-05002019-05-011211610.1186/s13104-019-4337-6Evaluating the influence of common antibiotics on the efficacy of a recombinant immunotoxin in tissue cultureYuyi Zhu0John E. Weldon1Department of Biological Sciences, The Jess and Mildred Fisher College of Science and Mathematics, Towson UniversityDepartment of Biological Sciences, The Jess and Mildred Fisher College of Science and Mathematics, Towson UniversityAbstract 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.http://link.springer.com/article/10.1186/s13104-019-4337-6Recombinant immunotoxinsCombination therapyAntibioticsHB21-LRPseudomonas exotoxin ACytotoxicity |
| spellingShingle | Yuyi Zhu John E. Weldon Evaluating the influence of common antibiotics on the efficacy of a recombinant immunotoxin in tissue culture BMC Research Notes Recombinant immunotoxins Combination therapy Antibiotics HB21-LR Pseudomonas exotoxin A Cytotoxicity |
| title | Evaluating the influence of common antibiotics on the efficacy of a recombinant immunotoxin in tissue culture |
| title_full | Evaluating the influence of common antibiotics on the efficacy of a recombinant immunotoxin in tissue culture |
| title_fullStr | Evaluating the influence of common antibiotics on the efficacy of a recombinant immunotoxin in tissue culture |
| title_full_unstemmed | Evaluating the influence of common antibiotics on the efficacy of a recombinant immunotoxin in tissue culture |
| title_short | Evaluating the influence of common antibiotics on the efficacy of a recombinant immunotoxin in tissue culture |
| title_sort | evaluating the influence of common antibiotics on the efficacy of a recombinant immunotoxin in tissue culture |
| topic | Recombinant immunotoxins Combination therapy Antibiotics HB21-LR Pseudomonas exotoxin A Cytotoxicity |
| url | http://link.springer.com/article/10.1186/s13104-019-4337-6 |
| work_keys_str_mv | AT yuyizhu evaluatingtheinfluenceofcommonantibioticsontheefficacyofarecombinantimmunotoxinintissueculture AT johneweldon evaluatingtheinfluenceofcommonantibioticsontheefficacyofarecombinantimmunotoxinintissueculture |