cGMP production of astatine-211-labeled anti-CD45 antibodies for use in allogeneic hematopoietic cell transplantation for treatment of advanced hematopoietic malignancies

Journal Article · Thu Oct 18 00:00:00 EDT 2018 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0205135· OSTI ID:1478137

Li, Yawen; Hamlin, Donald K.; Chyan, Ming-Kuan; Wong, Roger; Dorman, Eric F.; Emery, Robert C.; Woodle, Douglas R.; Manger, Ronald L.; Nartea, Margaret; Kenoyer, Aimee L.; Orozco, Johnnie J.; Green, Damian J.; Press, Oliver W.; Storb, Rainer; Sandmaier, Brenda M.; Wilbur, D. Scott ; Fassbender, ed., Michael Ernst-Heinrich

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-phe-nethyl-closo-decaborate(2-) (B10-NCS), (2) anti-CD45 MAb, BC8, (3) BC8-B10 MAb conju-gate, (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 <0.50 EU/mL. Cell binding was retained by the ²¹¹At-BC8-B10. ²¹¹At-BC8-B10 in ascorbic acid solution demonstrated a radiochemical stability of >95% for up to 21 h at room temperature. The experiments conducted have defined conditions for translation of ²¹¹At-BC8-B10 production

• Research Organization: Univ. of Washington, Seattle, WA (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Nuclear Physics (NP)
• Grant/Contract Number: SC0012618; SC0013618
• OSTI ID: 1478137
• Alternate ID(s): OSTI ID: 1483573
• Journal Information: PLoS ONE, Journal Name: PLoS ONE Vol. 13 Journal Issue: 10; ISSN 1932-6203
• Publisher: Public Library of Science (PLoS)
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES