title: Bovine apolipoprotein B-100 is a dominant immunogen in therapeutic cell populations cultured in fetal calf serum in mice and humans.
abstract: 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 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.
authors: Division of Therapeutic Proteins, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA.
authors: Norihisa
authors: N
authors: Sakamoto
authors: Kazuhide
authors: K
authors: Tsuji
authors: Linda M
authors: LM
authors: Muul
authors: Ann M
authors: AM
authors: Lawler
authors: Emanuel F
authors: EF
authors: Petricoin
authors: Fabio
authors: F
authors: Candotti
authors: Julia A
authors: JA
authors: Metcalf
authors: Jorge A
authors: JA
authors: Tavel
authors: H Clifford
authors: HC
authors: Lane
authors: Walter J
authors: WJ
authors: Urba
authors: Bernard A
authors: BA
authors: Fox
authors: Ajit
authors: A
authors: Varki
authors: Joan K
authors: JK
authors: Lunney
authors: Amy S
authors: AS
authors: Rosenberg
mesh_terms: D000818:Animals; D000917:Antibody Formation; D015478:Antigens, Heterophile / Q000276:immunology; D053299:Apolipoprotein B-100 / Q000276:immunology*; D001771:Blood Banks; D002417:Cattle; D053595:Embryonic Stem Cells / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains / Q000276:immunology; D008822:Mice, Transgenic; D009316:National Institutes of Health (U.S.); D014481:United States; D014612:Vaccines
chemical_list: D015478:Antigens, Heterophile; D053299:Apolipoprotein B-100; D014612:Vaccines