Bovine apolipoprotein B-100 is a dominant immunogen in therapeutic cell populations cultured in fetal calf serum in mice and humans.
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.
Sakamoto
Norihisa
N
Division of Therapeutic Proteins, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA.
Tsuji
Kazuhide
K
Muul
Linda M
LM
Lawler
Ann M
AM
Petricoin
Emanuel F
EF
Candotti
Fabio
F
Metcalf
Julia A
JA
Tavel
Jorge A
JA
Lane
H Clifford
HC
Urba
Walter J
WJ
Fox
Bernard A
BA
Varki
Ajit
A
Lunney
Joan K
JK
Rosenberg
Amy S
AS
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
D015478:Antigens, Heterophile; D053299:Apolipoprotein B-100; D014612:Vaccines