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Blood, 15 July 2007, Vol. 110, No. 2, pp. 501-508.
Prepublished online as a Blood First Edition Paper on March 29, 2007; DOI 10.1182/blood-2007-01-066522.


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Submitted January 5, 2007
Accepted March 24, 2007

Bovine apolipoprotein B-100 is a dominant immunogen in therapeutic cell populations cultured in FCS in mice and humans

Norihisa Sakamoto, Kazuhide Tsuji, Linda M. Muul, Ann M. Lawler, Emanuel F. Petricoin, Fabio Candotti, Julia A. Metcalf, Jorge A. Tavel, H. Clifford Lane, Walter J. Urba, Bernard A. Fox, Ajit Varki, Joan K. Lunney, and Amy S. Rosenberg*

Division of Therapeutic Proteins, CDER, U.S. Food and Drug Administration, Bethesda, MD, United States
Department of Dermatology, Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical Sciences, Okayama, Japan
Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
Transgenic Mouse Facility and Department of Physiology, Johns Hopkins University, School of Medicine, Baltimore, MD, United States
Center for Applied Proteomics and Molecular Medicine, Dept of Molecular & Microbiology, George Mason University, Manassas, VA, United States
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
Laboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Research Center, Earle A Chiles Research Institute, Portland Medical Center, Portland, OR, United States
Glycobiology Research and Training Center, and Depts of Medicine and Cellular & Molecular Medicine, University of California, San Diego, CA, United States
Animal Parasitic Diseases Laboratory, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD, United States

* Corresponding author; email: amy.rosenberg{at}fda.gov.

Recent studies have demonstrated that cell populations intended for therapeutic purposes that are cultured in heterologous animal products can acquire xenoantigens, potentially limiting their utility. In investigations of the immune response to murine embryonic stem (ES) cells, we found that a strong antibody response was generated after the second infusion. Both polyclonal and monoclonal antibody responses, derived from immunized mice, were found to be specific for bovine apolipoprotein B-100 which binds to abundant low density lipoprotein receptor on the cell surface and is internalized. Here we have shown that in the majority of patients administered three different types of cell-based therapies utilizing cells grown in FCS containing media, an antibody response to bovine apoB-100 develops following the second infusion and is the dominant specificity. The known and potential clinical effects of such antibodies are discussed.


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Stem CellsHome page
M. Hisamatsu-Sakamoto, N. Sakamoto, and A. S. Rosenberg
Embryonic Stem Cells Cultured in Serum-Free Medium Acquire Bovine Apolipoprotein B-100 from Feeder Cell Layers and Serum Replacement Medium
Stem Cells, January 1, 2008; 26(1): 72 - 78.
[Abstract] [Full Text] [PDF]



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