Academic Journal
cGMP production of astatine-211-labeled anti-CD45 antibodies for use in allogeneic hematopoietic cell transplantation for treatment of advanced hematopoietic malignancies.
| Title: | cGMP production of astatine-211-labeled anti-CD45 antibodies for use in allogeneic hematopoietic cell transplantation for treatment of advanced hematopoietic malignancies. |
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| Authors: | Yawen Li, Donald K Hamlin, Ming-Kuan Chyan, Roger Wong, Eric F Dorman, Robert C Emery, Douglas R Woodle, Ronald L Manger, Margaret Nartea, Aimee L Kenoyer, Johnnie J Orozco, Damian J Green, Oliver W Press, Rainer Storb, Brenda M Sandmaier, D Scott Wilbur |
| Source: | PLoS ONE, Vol 13, Iss 10, p e0205135 (2018) |
| Publisher Information: | Public Library of Science (PLoS), 2018. |
| Publication Year: | 2018 |
| Collection: | LCC:Medicine LCC:Science |
| Subject Terms: | Medicine, Science |
| More Details: | The objective of this study was to translate reaction conditions and quality control methods used for production of an astatine-211(211At)-labeled anti-CD45 monoclonal antibody (MAb) conjugate, 211At-BC8-B10, from the laboratory setting to cGMP production. Five separate materials were produced in the preparation of 211At-BC8-B10: (1) p-isothiocyanato-phenethyl-closo-decaborate(2-) (B10-NCS), (2) anti-CD45 MAb, BC8, (3) BC8-B10 MAb conjugate, (4) [211At]NaAt, and (5) 211At-BC8-B10. The 211At-labeling reagent, B10-NCS, was synthesized as previously reported. BC8 was produced, then conjugated with B10-NCS under cGMP conditions to form BC8-B10. [211At]NaAt was produced by α-irradiation of Bi targets, followed by isolation of the 211At using a "wet chemistry" method. The clinical product, 211At-BC8-B10, was prepared by reacting [211At]NaAt with BC8-B10 in NH4OAc buffer (pH 5.5) for 2 min at room temperature, followed by size-exclusion chromatography purification. Quality control tests conducted on the 211At-BC8-B10 included evaluations for purity and identity, as well as pyrogen and sterility tests. Stability of the 211At-BC8-B10 in 25 mg/mL sodium ascorbate solution was evaluated at 1, 2, 4, 6 and 21 h post isolation. For qualification, three consecutive 211At-BC8-B10 clinical preparations were successfully conducted in the cGMP suite, and an additional cGMP clinical preparation was carried out to validate each step required to deliver 211At-BC8-B10 to a patient. These cGMP preparations provided 0.80-1.28 Gbq (21.5-34.5 mCi) of 211At-BC8-B10 with radiochemical purity of >97%. The preparations were found to be sterile and have a pyrogen level 95% for up to 21 h at room temperature. The experiments conducted have defined conditions for translation of 211At-BC8-B10 production from the laboratory to cGMP suite. This study has allowed the initiation of a phase I/II clinical trial using 211At-BC8-B10 (NCT03128034). |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1932-6203 |
| Relation: | http://europepmc.org/articles/PMC6193629?pdf=render; https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0205135 |
| Access URL: | https://doaj.org/article/cbfd877a8a544580afae3b17128483ad |
| Accession Number: | edsdoj.bfd877a8a544580afae3b17128483ad |
| Database: | Directory of Open Access Journals |
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| ISSN: | 19326203 |
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| DOI: | 10.1371/journal.pone.0205135 |
| Published in: | PLoS ONE |
| Language: | English |