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Title: Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model

Abstract

Alpha emitting radionuclides release a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD) conditions in which micrometastatic disease satellites are broadly distributed. To evaluate this hypothesis, 211At conjugated 1F5 mAb (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to 211At conjugated 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor bearing animals treated with doses of up to 48µCi of anti-CD20 211At-decaborate [211At-B10-1F5] experienced modest responses (0% cures but 2-3-fold prolongation of survival compared to negative controls). In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with 211At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity is observed in the cured animals receiving 15 µCi of 211At-B10-1F5. These findings suggest that in a MRD lymphoma model, where isolated cells and tumor microclusters prevail, α-emitters may be uniquely efficacious.

Authors:
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Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1221465
Report Number(s):
PNNL-SA-107680
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Blood, 125(13):2111-2119
Country of Publication:
United States
Language:
English
Subject:
1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

Citation Formats

Green, Damian J., Shadman, Mazyar, Jones, Jon C., Frayo, Shani, Kenoyer, Aimee L., Hylarides, Mark, Hamlin, Donald K., Wilbur, D. Scott, Balkan, Ethan R., Lin, Yukang, Miller, Brian W., Frost, Sophia, Gopal, Ajay K., Orozco, Johnnie J., Gooley, Ted, Laird, Kelley L., Till, B. G., Back, Tom, Sandmaier, B. M., Pagel, John M., and Press, Oliver W. Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model. United States: N. p., 2015. Web. doi:10.1182/blood-2014-11-612770.
Green, Damian J., Shadman, Mazyar, Jones, Jon C., Frayo, Shani, Kenoyer, Aimee L., Hylarides, Mark, Hamlin, Donald K., Wilbur, D. Scott, Balkan, Ethan R., Lin, Yukang, Miller, Brian W., Frost, Sophia, Gopal, Ajay K., Orozco, Johnnie J., Gooley, Ted, Laird, Kelley L., Till, B. G., Back, Tom, Sandmaier, B. M., Pagel, John M., & Press, Oliver W. Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model. United States. doi:10.1182/blood-2014-11-612770.
Green, Damian J., Shadman, Mazyar, Jones, Jon C., Frayo, Shani, Kenoyer, Aimee L., Hylarides, Mark, Hamlin, Donald K., Wilbur, D. Scott, Balkan, Ethan R., Lin, Yukang, Miller, Brian W., Frost, Sophia, Gopal, Ajay K., Orozco, Johnnie J., Gooley, Ted, Laird, Kelley L., Till, B. G., Back, Tom, Sandmaier, B. M., Pagel, John M., and Press, Oliver W. Thu . "Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model". United States. doi:10.1182/blood-2014-11-612770.
@article{osti_1221465,
title = {Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model},
author = {Green, Damian J. and Shadman, Mazyar and Jones, Jon C. and Frayo, Shani and Kenoyer, Aimee L. and Hylarides, Mark and Hamlin, Donald K. and Wilbur, D. Scott and Balkan, Ethan R. and Lin, Yukang and Miller, Brian W. and Frost, Sophia and Gopal, Ajay K. and Orozco, Johnnie J. and Gooley, Ted and Laird, Kelley L. and Till, B. G. and Back, Tom and Sandmaier, B. M. and Pagel, John M. and Press, Oliver W.},
abstractNote = {Alpha emitting radionuclides release a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD) conditions in which micrometastatic disease satellites are broadly distributed. To evaluate this hypothesis, 211At conjugated 1F5 mAb (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to 211At conjugated 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor bearing animals treated with doses of up to 48µCi of anti-CD20 211At-decaborate [211At-B10-1F5] experienced modest responses (0% cures but 2-3-fold prolongation of survival compared to negative controls). In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with 211At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity is observed in the cured animals receiving 15 µCi of 211At-B10-1F5. These findings suggest that in a MRD lymphoma model, where isolated cells and tumor microclusters prevail, α-emitters may be uniquely efficacious.},
doi = {10.1182/blood-2014-11-612770},
journal = {Blood, 125(13):2111-2119},
number = ,
volume = ,
place = {United States},
year = {Thu Mar 26 00:00:00 EDT 2015},
month = {Thu Mar 26 00:00:00 EDT 2015}
}