Potent anti-tumor activity of CD45RA-targeting Hm3A4-Ranpirnase against myeloid lineage leukemias.
CD45RA
Hm3A4
Immunotoxin
leukemic stem cells
ranpirnase
targeting therapy
Journal
Bioengineered
ISSN: 2165-5987
Titre abrégé: Bioengineered
Pays: United States
ID NLM: 101581063
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
entrez:
24
3
2022
pubmed:
25
3
2022
medline:
27
4
2022
Statut:
ppublish
Résumé
CD45RA is a specific marker for leukemia stem cell (LSC) sub-populations in acute myeloid leukemia (AML). Ranpirnase (Rap), an amphibian RNase, has been extensively investigated in preclinical and clinical studies for its antitumor activity. Rap could be administered repeatedly to patients without inducing an immune response. Reversible renal toxicity has been reported to be dose-limiting. In this study, we generated a novel immunotoxin targeting LSCs: Hm3A4-Rap, which was composed of Rap and Hm3A4, a human-mouse chimeric antibody against CD45RA. This immunotoxin was generated recombinantly by fusing Rap to Hm3A4 at the Fc terminus and then produced by stably transfecting CHO cells. The immunotoxin was purified using Ni-NTA and then evaluated using RT-PCR, SDS-PAGE, antibody titer assays, competitive inhibition assays, and internalization assays. In addition, the purity, molecular integrity, and affinity to the CD45RA antigen were determined.
Identifiants
pubmed: 35322728
doi: 10.1080/21655979.2022.2054159
pmc: PMC9161826
doi:
Substances chimiques
Immunotoxins
0
Ribonucleases
EC 3.1.-
ranpirnase
ZE15FIT23E
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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