Haagen I A, van de Griend R, Clark M, Geerars A, Bast B, de Gast B
Department of Clinical Immunology, University Hospital Utrecht, The Netherlands.
Clin Exp Immunol. 1992 Dec;90(3):368-75. doi: 10.1111/j.1365-2249.1992.tb05853.x.
Bispecific antibodies (BsAb) can be used to retarget T cells irrespective of their specificity to certain target cells inducing target cell lysis. We have tested the efficacy of the BsAb SHR-1, directed against the T cell antigen CD3 and the B cell antigen CD19 to induce (malignant) B cell kill by T cells as measured in a 51Cr-release assay. Two cytotoxic T cell clones (CTL), expressing TCR alpha beta or TCR gamma delta, were effective in killing CD19 expressing B cell lines at different stages of differentiation in the presence, but not in the absence, of the BsAb. CD19- target cells were not killed. Fresh CD19+ leukaemia/lymphoma cells were also efficiently killed by SHR-1 preincubated CTL clones. In addition, phytohaemagglutinin (PHA) or CD3-activated IL-2 expanded peripheral blood mononuclear cells (PBMC) of normal donors did so after 2 weeks of stimulation. A concentration of 100 ng/ml of the BsAb was sufficient to obtain optimal lysis of all target cells tested. These results show that fresh human leukaemia/lymphoma cells, freshly derived from active lymphoblastic leukaemia (ALL) as well as non-Hodgkin's lymphoma (NHL) patients, can be effectively killed in the presence of this BsAb by activated T cells.
双特异性抗体（BsAb）可用于重新靶向T细胞，无论其对某些靶细胞的特异性如何，均可诱导靶细胞裂解。我们已经测试了双特异性抗体SHR-1的功效，该抗体针对T细胞抗原CD3和B细胞抗原CD19，通过51Cr释放试验来测定其诱导T细胞杀伤（恶性）B细胞的能力。两个表达TCRαβ或TCRγδ的细胞毒性T细胞克隆（CTL），在存在双特异性抗体的情况下，而非不存在时，能够有效杀伤处于不同分化阶段的表达CD19的B细胞系。不表达CD19的靶细胞未被杀伤。预先用SHR-1孵育的CTL克隆也能有效杀伤新鲜的CD19+白血病/淋巴瘤细胞。此外，正常供体的经植物血凝素（PHA）或CD3激活的白细胞介素-2扩增的外周血单个核细胞（PBMC）在刺激2周后也能做到这一点。100 ng/ml的双特异性抗体浓度足以实现对所有测试靶细胞的最佳裂解。这些结果表明，源自急性淋巴细胞白血病（ALL）以及非霍奇金淋巴瘤（NHL）患者的新鲜人白血病/淋巴瘤细胞，在这种双特异性抗体存在的情况下，可被活化的T细胞有效杀伤。
