MURINE ANTI-MOUSE T-CELL MONOCLONAL-ANTIBODIES ELICIT ANTI-ANTIBODIESIN MICE - INTRASPECIES IMMUNIZATION MODEL FOR ESTIMATING POTENTIAL PATIENT SENSITIZATION AGAINST HUMANIZED ANTI-T-CELL ANTIBODIES

Humanization of immunosuppressive anti-T cell monoclonal antibodies (m Ab) raises the question as to how completely it helps to avoid formati on of neutralizing anti-antibodies (anti-Ab) in patients. To get more information on intra-species sensitization against anti-T cell mAb, we produced two immunosuppressive mouse IgG2a anti-mouse Thy-1.2 mAb (Mm T1 and MmT5) in AKR/J mice and measured the potential of MmT1 to elici t inhibitory anti-Ab in AKR/J (H-2k), C57BL/6 (H-2b), congenic B10.BR (H-2k) and DBA/2 (H-2d) mice. After one injection once weekly for 4 we eks of 5 mug MmT1 (200 mug/kg) in C57BL/6 mice, without the use of any adjuvants, high concentrations of anti-Ab directed against MmT1 (300 mug/ml) and MmT5 (100 mug/ml) were measured by enzyme-linked immunosor bent assay. Similar concentrations of anti-Ab were found in immunized DBA/2 and less in B10.BR mice. No syngeneic anti-Ab could be produced in AKR/J. From the C57BL/6 mice, we raised anti-MmT1+, MmT5-idiotype ( IDIO1) and anti-MmT1+, MmT5+ allotype (ALLO1) mAb. An in vivo test sys tem was adapted to measure the inhibitory effects of circulating poly- or monoclonal anti-Ab. It revealed a reduction of in vivo depletion c apacity not only of the sensitizing mAb (MmT1), but also of another an ti-Thy-1.2 mAb (MmT5), with identical allotype but different idiotype. From this we conclude that intra-species immunization following injec tion of anti-T cell mAb can produce high titer inhibitory anti-idiotyp e and anti-allotype antibodies. Implications for hyperchimeric or full y human anti-T cell mAb are discussed.