TY - JOUR
T1 - Human monoclonal antibodies specific to hepatitis B virus generated in a human/mouse radiation chimera
T2 - The Trimera system
AU - Eren, R.
AU - Lubin, I.
AU - Terkieltaub, D.
AU - Ben-Moshe, O.
AU - Zauberman, A.
AU - Uhlmann, R.
AU - Tzahor, T.
AU - Moss, S.
AU - Ilan, E.
AU - Shouval, D.
AU - Galun, E.
AU - Daudi, N.
AU - Marcus, H.
AU - Reisner, Y.
AU - Dagan, S.
PY - 1998
Y1 - 1998
N2 - An approach to develop fully human monoclonal antibodies in a human/mouse radiation chimera, the Trimera system, is described. In this system, functional human lymphocytes are engrafted in normal strains of mice which are rendered immuno-incompetent by lethal total body irradiation followed by radioprotection with severe combined immunodeficient (SCID) mouse bone marrow. Following transplantation, human lymphocytes colonize murine lymphatic organs and secrete human immunoglobulins. We have established this system as a tool to develop fully human monoclonal antibodies, and applied it for the generation of monoclonal antibodies specific for hepatitis B virus surface antigen. A strong memory response to hepatitis B surface antigen was elicited in Trimera engrafted with lymphocytes from human donors positive for antibodies to hepatitis B surface antigen. The human specific antibody fraction in the Trimera was 102-103-fold higher as compared with that found in the donors. Spleens were harvested from Trimera mice showing high specific-antibody titres and cells were fused to a human-mouse heteromyeloma fusion partner. Several stable hybridoma clones were isolated and characterized. These hybridomas produce high-affinity, IgG, anti-hepatitis B surface antigen antibodies demonstrating the potential of the Trimera system for generating fully human monoclonal antibodies. The biological function and the neutralizing activity of these antibodies are currently being tested.
AB - An approach to develop fully human monoclonal antibodies in a human/mouse radiation chimera, the Trimera system, is described. In this system, functional human lymphocytes are engrafted in normal strains of mice which are rendered immuno-incompetent by lethal total body irradiation followed by radioprotection with severe combined immunodeficient (SCID) mouse bone marrow. Following transplantation, human lymphocytes colonize murine lymphatic organs and secrete human immunoglobulins. We have established this system as a tool to develop fully human monoclonal antibodies, and applied it for the generation of monoclonal antibodies specific for hepatitis B virus surface antigen. A strong memory response to hepatitis B surface antigen was elicited in Trimera engrafted with lymphocytes from human donors positive for antibodies to hepatitis B surface antigen. The human specific antibody fraction in the Trimera was 102-103-fold higher as compared with that found in the donors. Spleens were harvested from Trimera mice showing high specific-antibody titres and cells were fused to a human-mouse heteromyeloma fusion partner. Several stable hybridoma clones were isolated and characterized. These hybridomas produce high-affinity, IgG, anti-hepatitis B surface antigen antibodies demonstrating the potential of the Trimera system for generating fully human monoclonal antibodies. The biological function and the neutralizing activity of these antibodies are currently being tested.
UR - http://www.scopus.com/inward/record.url?scp=6844258881&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2567.1998.00426.x
DO - 10.1046/j.1365-2567.1998.00426.x
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 9616363
AN - SCOPUS:6844258881
SN - 0019-2805
VL - 93
SP - 154
EP - 161
JO - Immunology
JF - Immunology
IS - 2
ER -
