IMMUNOSUPPRESSION - PRE-CLINICAL AGENTS

H.R. Cho¹, J.S. Lee², S. Lee³, B. Kwon^4
1Surgery, Ulsan University Hospital , , Ulsan/KOREA, ²Internal Medicine, Ulsan University Hospital ,, Ulsan/KOREA, ³Surgery, Ulsan University Hospital ,, Ulsan/KOREA, ⁴School Of Biological Sciences, University of Ulsan, Ulsan/KOREA

Body: CD137 is expressed on activated T cells and is believed to be a reliable surrogate marker for antigen-specific T cells. In this study, we wanted to examine the possibility for toxin-conjugated anti-CD137 monoclonal antibody (mAb) to kill CD137-expressing T cells. We conjugated doxorubicin to anti-CD137 mAb and tested its efficacy to kill T cells in vitro and in vivo. We found that anti-mouse CD137 mAb was internalized into CD137-expressing cell lines and primary T cells via endocytosis. Similarly, anti-human CD137 mAb was internalized into primary human or monkey T cells. Doxorubicin-conjugated anti-CD137 mAb preferentially killed CD137-expressing primary T cells, confirming its specificity. In vivo treatment of doxorubicin-conjugated anti-CD137 mAb was effective in deleting alloreactive T cells and inhibiting graft-versus-host disease (GVHD). When we used complexes of anti-CD137 and saporin, an inhibitor of protein synthesis, we observed a similar or more potent killing activity of these antibody-toxin complexes against alloreactive or xenoreactive primary human, monkey, or mouse T cells. Our results indicate that CD137-targeted delivery of toxin is a good strategy to delete allo- or xenoreactive T cells. This approach may be used to block allo- or xenoagraft rejection.

Disclosure: All authors have declared no conflicts of interest.