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

Author:

Sakamoto Norihisa1,Tsuji Kazuhide12,Muul Linda M.3,Lawler Ann M.4,Petricoin Emanuel F.5,Candotti Fabio3,Metcalf Julia A.6,Tavel Jorge A.6,Lane H. Clifford6,Urba Walter J.7,Fox Bernard A.7,Varki Ajit8,Lunney Joan K.9,Rosenberg Amy S.1

Affiliation:

1. Division of Therapeutic Proteins, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD;

2. Department of Dermatology, Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical Sciences, Japan;

3. Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD;

4. Transgenic Mouse Facility and Department of Physiology, Johns Hopkins University, School of Medicine, Baltimore, MD;

5. Center for Applied Proteomics and Molecular Medicine, Department of Molecular and Microbiology, George Mason University, Manassas, VA;

6. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;

7. Laboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR;

8. Glycobiology Research and Training Center and Departments of Medicine and Cellular and Molecular Medicine, University of California, San Diego;

9. Animal Parasitic Diseases Laboratory, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD

Abstract

AbstractRecent 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 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 receptors on the cell surface and is internalized. Here we show that in the majority of patients administered 3 different types of cell-based therapies using cells grown in fetal calf serum-containing media, an antibody response to bovine apolipoprotein B-100 develops after the second infusion and is the dominant specificity. The known and potential clinical effects of such antibodies are discussed.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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