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

Author
item SAKAMOTO, NORIHISA - BETHESDA, MD
item TUJI, KUZUHIDE - OKAYAMA, JAPAN
item MUUL, LINDA - NIH BETHESDA, MD
item LAWLER, ANN - JOHNS HOPKINS,BALTIMORE
item CANDOTTI, FABIO - NIH BETHESDA, MD
item METCALF, JULIA - NIH BETHESDA, MD
item TAVEL, JORGE - NIH BETHESDA, MD
item LANE, H. CLIFFORD - NIH BETHESDA.
item URBA, WALTER - PORTLAND, OREGON
item FOX, BERNARD - PORTLAND, OREGON
item VARKI8, AJIT - U CALIFORNIA LA JOLLA
item Lunney, Joan
item ROSENBERG, AMY - NIH BETHESDA, MD

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 3/15/2007
Publication Date: 3/19/2007
Citation: Sakamoto, N., Tuji, K., Muul, L.M., Lawler, A.M., Candotti, F., Metcalf, J.A., Tavel, J.A., Lane, H.C., Urba, W.J., Fox, B.A., Varki8, A.P., Lunney, J.K., Rosenberg, A.S. 2007. : bovine apolipoprotein b-100 is a dominant immunogen in therapeutic cell populations cultured in fcs in mice and humans. J. Immunol., 178: 88.29.

Interpretive Summary:

Technical 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 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. Critically, 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 low level of engraftment of genetically modified autologous cells in an ADA-SCID patient with a strong bovine apoB response suggests that such antibodies may influence cell engraftment.