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

Abstract

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 stepmore » 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« less

Authors:
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Publication Date:
Research Org.:
Univ. of Washington, Seattle, WA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Nuclear Physics (NP) (SC-26)
OSTI Identifier:
1478137
Alternate Identifier(s):
OSTI ID: 1483573
Grant/Contract Number:  
SC0012618; SC0013618
Resource Type:
Published Article
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Name: PLoS ONE Journal Volume: 13 Journal Issue: 10; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science (PLoS)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

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, and Fassbender, ed., Michael Ernst-Heinrich. cGMP production of astatine-211-labeled anti-CD45 antibodies for use in allogeneic hematopoietic cell transplantation for treatment of advanced hematopoietic malignancies. United States: N. p., 2018. Web. doi:10.1371/journal.pone.0205135.
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. cGMP production of astatine-211-labeled anti-CD45 antibodies for use in allogeneic hematopoietic cell transplantation for treatment of advanced hematopoietic malignancies. United States. doi:10.1371/journal.pone.0205135.
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, and Fassbender, ed., Michael Ernst-Heinrich. Thu . "cGMP production of astatine-211-labeled anti-CD45 antibodies for use in allogeneic hematopoietic cell transplantation for treatment of advanced hematopoietic malignancies". United States. doi:10.1371/journal.pone.0205135.
@article{osti_1478137,
title = {cGMP production of astatine-211-labeled anti-CD45 antibodies for use in allogeneic hematopoietic cell transplantation for treatment of advanced hematopoietic malignancies},
author = {Li, Yawen and Hamlin, Donald K. and Chyan, Ming-Kuan and Wong, Roger and Dorman, Eric F. and Emery, Robert C. and Woodle, Douglas R. and Manger, Ronald L. and Nartea, Margaret and Kenoyer, Aimee L. and Orozco, Johnnie J. and Green, Damian J. and Press, Oliver W. and Storb, Rainer and Sandmaier, Brenda M. and Wilbur, D. Scott and Fassbender, ed., Michael Ernst-Heinrich},
abstractNote = {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},
doi = {10.1371/journal.pone.0205135},
journal = {PLoS ONE},
number = 10,
volume = 13,
place = {United States},
year = {2018},
month = {10}
}

Journal Article:
Free Publicly Available Full Text
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DOI: 10.1371/journal.pone.0205135

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    New Synthesis Method of N-Monosubstituted Ammonium-closo-Decaborates
    journal, July 2019