Biomarkers Unit, Department of Applied Research and Technical Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Human Tumor Immunobiology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Front Immunol. 2019 Oct 25;10:2514. doi: 10.3389/fimmu.2019.02514. eCollection 2019.
T-cell-based immunotherapy strategies have profoundly improved the clinical management of several solid tumors and hematological malignancies. A recently developed and promising immunotherapy approach is to redirect polyclonal MHC-unrestricted T lymphocytes toward cancer cells by bispecific antibodies (bsAbs) that engage the CD3 complex and a tumor-associated antigen (TAA). The TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) is an attractive immunotherapy target, frequently expressed by neoplastic cells, that we decided to exploit as a TAA. We found that a TRAIL-R2xCD3 bsAb efficiently activates T cells and specifically redirect their cytotoxicity against cancer cells of different origins , thereby demonstrating its potential as a pan-carcinoma reagent. Moreover, to mimic conditions, we assessed its ability to retarget T-cell activity in an model of ovarian cancer patients' ascitic fluids containing both effector and target cells-albeit with a suboptimal effector-to-target ratio-with remarkable results.
基于 T 细胞的免疫疗法策略极大地改善了几种实体瘤和血液恶性肿瘤的临床治疗。最近开发的一种很有前途的免疫治疗方法是通过双特异性抗体（bsAb）将多克隆 MHC 无限制的 T 淋巴细胞重定向到癌细胞，该 bsAb 与 CD3 复合物和肿瘤相关抗原（TAA）结合。TNF 相关凋亡诱导配体受体 2（TRAIL-R2）是一种有吸引力的免疫治疗靶点，经常在肿瘤细胞中表达，我们决定将其作为 TAA 加以利用。我们发现，TRAIL-R2xCD3 bsAb 能够有效地激活 T 细胞，并特异性地将其细胞毒性重定向到不同来源的癌细胞，从而证明其作为泛癌试剂的潜力。此外，为了模拟体内条件，我们评估了它在含有效应细胞和靶细胞的卵巢癌患者腹水模型中重新靶向 T 细胞活性的能力，尽管效应细胞与靶细胞的比例不理想，但结果显著。
