Haagen I A, de Lau W B, Bast B J, Geerars A J, Clark M R, de Gast B C
Department of Immunology, University Hospital of Utrecht, The Netherlands.
Cancer Immunol Immunother. 1994 Dec;39(6):391-6. doi: 10.1007/BF01534426.
We previously reported that a CD3 x CD19 bispecific antibody (bsAb) can induce efficient killing of tumour cells by preactivated T cells isolated from patients with B cell malignancy. For future intravenous application we investigated whether resting T cells from peripheral blood can be stimulated to proliferate and become cytotoxic with the CD3 x CD19 bsAb alone. Indeed peripheral blood mononuclear cells, isolated from healthy donors or patients with B cell malignancy, started to proliferate within 1 day in response to CD3 x CD19 bsAb. Within the same time span cytotoxic activity against CD19-positive tumour cells was already detectable. Maintenance of cytotoxic activity was seen during 3 days of culture but optimal lysis of the target cells then required fresh CD3 x CD19 bsAb in the cytotoxicity assay. Essentially the same results for proliferation and cytotoxicity were found when separated CD4-positive and CD8-positive T cells were activated by the bsAb in the presence of autologous monocytes. These results may be relevant for the in vivo application of the bsAb when used as immunotherapy in patients with B cell malignancy.
我们之前报道过，一种CD3×CD19双特异性抗体（bsAb）能够通过从B细胞恶性肿瘤患者中分离出的预激活T细胞高效杀伤肿瘤细胞。为了未来的静脉内应用，我们研究了外周血中的静息T细胞是否仅用CD3×CD19 bsAb就能被刺激增殖并变得具有细胞毒性。实际上，从健康供体或B细胞恶性肿瘤患者中分离出的外周血单个核细胞，在接触CD3×CD19 bsAb后1天内就开始增殖。在同一时间段内，针对CD19阳性肿瘤细胞的细胞毒性活性已经可以检测到。在培养的3天内观察到细胞毒性活性得以维持，但在细胞毒性试验中，随后靶细胞的最佳裂解需要新鲜的CD3×CD19 bsAb。当分离的CD4阳性和CD8阳性T细胞在自体单核细胞存在的情况下被bsAb激活时，在增殖和细胞毒性方面发现了基本相同的结果。这些结果对于bsAb在B细胞恶性肿瘤患者中用作免疫疗法的体内应用可能具有重要意义。
