尽管自然杀伤 (NK) 细胞在治疗血液恶性肿瘤方面取得了良好的效果，但在卵巢癌 (OvCa) 等实体瘤中的疗效有限。在此，我们评估了表达变体白细胞介素 2 (vIL-2) 细胞因子的溶瘤腺病毒 Ad5/3-E2F-d24-vIL2（vIL-2 病毒）（也称为 TILT-452）增强 NK 细胞的潜力离体人 OvCa 的治疗效果。将人类 OvCa 手术标本加工成单细胞悬浮液，并从健康献血者中扩增 NK 细胞。 OvCa 样品消化物与 NK 细胞和 vIL-2 病毒进行离体共培养，并通过细胞阻抗测量实时评估癌细胞杀伤潜力。使用 OvCa 患者来源的异种移植物 (PDX) 在小鼠体内对所提出的治疗组合进行了体内评估。 vIL-2 病毒的添加显着增强了经过处理的 OvCa 共培养物中 NK 细胞治疗的杀伤潜力。同样，vIL-2病毒与NK细胞疗法相结合促进了体内OvCa肿瘤的最佳控制。从机制上讲，vIL-2病毒在NK细胞和CD8 T细胞中诱导更高比例的颗粒酶B，而T调节细胞比例在体内仍与NK细胞单一疗法相当。 Ad5/3-E2F-d24-vIL2 病毒治疗代表了一种有前途的策略，可增强人类 OvCa 中的过继 NK 细胞治疗效果。© 2023。作者。

Despite good results in the treatment of hematological malignancies, Natural killer (NK) cells have shown limited effectiveness in solid tumors, such as ovarian cancer (OvCa). Here, we assessed the potential of an oncolytic adenovirus expressing a variant interleukin-2 (vIL-2) cytokine, Ad5/3-E2F-d24-vIL2 (vIL-2 virus), also known as TILT-452, to enhance NK cell therapy efficacy in human OvCa ex vivo. Human OvCa surgical specimens were processed into single-cell suspensions and NK cells were expanded from healthy blood donors. OvCa sample digests were co-cultured ex vivo with NK cells and vIL-2 virus and cancer cell killing potential assessed in real time through cell impedance measurement. Proposed therapeutic combination was evaluated in vivo with an OvCa patient-derived xenograft (PDX) in mice. Addition of vIL-2 virus significantly enhanced NK cell therapy killing potential in treated OvCa co-cultures. Similarly, vIL-2 virus in combination with NK cell therapy promoted the best in vivo OvCa tumor control. Mechanistically, vIL-2 virus induced higher percentages of granzyme B in NK cells, and CD8+ T cells, while T regulatory cell proportions remained comparable to NK cell monotherapy in vivo. Ad5/3-E2F-d24-vIL2 virus treatment represents a promising strategy to boost adoptive NK cell therapeutic effect in human OvCa.© 2023. The Author(s).