MacLean J A, Su Z, Guo Y, Sy M S, Colvin R B, Wong J T
Department of Pathology, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
J Immunol. 1993 Feb 15;150(4):1619-28.
T cells are major mediators of graft rejection and many autoimmune diseases. During the Ag recognition process, T cells often become activated. We tested the hypothesis that an anti-CD3:anti-CD25 (CD3,25) bispecific mAb (BSMAB) can effectively and selectively target activated T cells. By flow cytometric analysis, the CD3,25 BSMAB was shown to bind avidly to activated T cells that coexpress CD3 and CD25 (p55 chain of the IL-2R), achieving higher levels than the parent anti-CD3 and anti-CD25 mAb. It bound only weakly to unstimulated T cells. The CD3,25 BSMAB effectively redirected CTL to lyse CD25-bearing PHA-stimulated T lymphoblasts and the IL2-dependent CTLL tumor cell line in chromium release assays. It was highly effective in blocking MLR as shown by inhibition of [3H]TdR incorporation. However, the CD3,25 BSMAB has a low potential to activate resting T cells, as it induced only minimal [3H]TdR incorporation even in the presence of exogenous IL-2. In the absence of exogenous IL-2, the CD3,25 BSMAB was unable to induce [3H]TdR incorporation. In contrast, the parent anti-CD3 mAb induced a high degree of incorporation. In summary, the CD3,25 BSMAB selectively targets activated CD25-expressing T cells and lymphomas although maintaining a low activation potential for unstimulated T cells, potentially advantageous properties that can be exploited for immunotherapy.
T细胞是移植排斥反应和许多自身免疫性疾病的主要介导者。在抗原识别过程中，T细胞常常被激活。我们检验了这样一个假设：抗CD3:抗CD25（CD3,25）双特异性单克隆抗体（BSMAB）能够有效且选择性地靶向激活的T细胞。通过流式细胞术分析，CD3,25 BSMAB被证明能与共表达CD3和CD25（IL-2R的p55链）的激活T细胞紧密结合，其结合水平高于亲本抗CD3和抗CD25单克隆抗体。它与未受刺激的T细胞仅有微弱结合。在铬释放试验中，CD3,25 BSMAB有效地重定向细胞毒性T淋巴细胞（CTL）以裂解表达CD25的PHA刺激的T淋巴母细胞和IL2依赖的CTLL肿瘤细胞系。如通过对[3H]TdR掺入的抑制所显示，它在阻断混合淋巴细胞反应（MLR）方面非常有效。然而，CD3,25 BSMAB激活静止T细胞的潜力较低，因为即使在存在外源性IL-2的情况下，它也仅诱导极少的[3H]TdR掺入。在没有外源性IL-2的情况下，CD3,25 BSMAB无法诱导[3H]TdR掺入。相反，亲本抗CD3单克隆抗体诱导了高度的掺入。总之，CD3,25 BSMAB选择性地靶向表达CD25的激活T细胞和淋巴瘤，同时对未受刺激的T细胞保持低激活潜力，这些潜在的有利特性可用于免疫治疗。
