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

Autor: Li Y; Department of Radiation Oncology, University of Washington, Seattle, Washington, United States of America., Hamlin DK; Department of Radiation Oncology, University of Washington, Seattle, Washington, United States of America., Chyan MK; Department of Radiation Oncology, University of Washington, Seattle, Washington, United States of America., Wong R; Department of Radiation Oncology, University of Washington, Seattle, Washington, United States of America., Dorman EF; Department of Radiation Oncology, University of Washington, Seattle, Washington, United States of America., Emery RC; Department of Radiation Oncology, University of Washington, Seattle, Washington, United States of America., Woodle DR; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America., Manger RL; Department of Medicine, University of Washington, Seattle, Washington, United States of America., Nartea M; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America., Kenoyer AL; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America., Orozco JJ; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America., Green DJ; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.; Department of Medicine, University of Washington, Seattle, Washington, United States of America., Press OW; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.; Department of Medicine, University of Washington, Seattle, Washington, United States of America., Storb R; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.; Department of Medicine, University of Washington, Seattle, Washington, United States of America., Sandmaier BM; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.; Department of Medicine, University of Washington, Seattle, Washington, United States of America., Wilbur DS; Department of Radiation Oncology, University of Washington, Seattle, Washington, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 Oct 18; Vol. 13 (10), pp. e0205135. Date of Electronic Publication: 2018 Oct 18 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0205135
Abstrakt: 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 <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 from the laboratory to cGMP suite. This study has allowed the initiation of a phase I/II clinical trial using 211At-BC8-B10 (NCT03128034).
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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