肿瘤细胞治疗研究
英文原题：A nanobody-based tri-specific NK cell engager targeting CD5 triggers antitumor immunity.
tri-NKCE 为 T 细胞恶性肿瘤提供了一种更安全且具成本效益的免疫疗法。
复发或难治性T细胞恶性肿瘤患者预后不良，凸显改善免疫治疗的必要性。CD5是恶性T细胞的特征性标志，几乎所有正常T细胞也表达CD5。因此，治疗T细胞恶性肿瘤时，聚焦于不表达CD5的自然杀伤（NK）细胞，可能比T细胞疗法更安全。我们通过特异性结合CD16a纳米抗体和高亲和力抗CD5抗体，构建靶向CD5的NK细胞衔接器（NKCE）。该分子在体外显示抗肿瘤效力。加入IL-15Rα/IL-15后，改良的三功能NKCE（tri-NKCE）对CD5+恶性肿瘤细胞的抗肿瘤作用更强，并产生更多细胞因子。体内实验显示，tri-NKCE通过促进NK细胞增殖增强细胞毒性。与CAR-T细胞相比，tri-NKCE不会对正常T细胞产生毒性。总之，tri-NKCE为治疗T细胞恶性肿瘤提供了一种更安全且成本效益较高的免疫疗法。
The poor prognosis of patients with recurrent or refractory T cell malignancies emphasizes the need for improved immunotherapies. CD5 is a characteristic marker of malignant T cells and is expressed on almost all normal T cells. Therefore, for treating T cell malignancies, focusing on natural killer (NK) cells lacking CD5 expression may elicit a better safety profile than that by T cell-based therapies. We generate a CD5-targeted NK cell engager (NKCE) through the specific binding of CD16a nanobody and a high-affinity anti-CD5 antibody. Its antitumor potency is demonstrated in vitro. After incorporating interleukin (IL)-15R /IL-15, the modified tri-NKCE exhibits stronger antitumor efficacy against CD5 + malignant tumor cells, with the production of more cytokines and chemokines. In vivo, tri-NKCE exhibits stronger cytotoxicity by enhancing NK cell proliferation. Compared with chimeric antigen receptor (CAR)-T cells, this tri-NKCE exhibits no toxicity to normal T cells. In conclusion, tri-NKCE offers a safer and cost-effective immunotherapy against T cell malignancies.
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