Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda 20892-1201, MD, USA.
J Immunother. 2011 Nov-Dec;34(9):651-61. doi: 10.1097/CJI.0b013e31823284c3.
Treatment of patients with adoptive T-cell therapy requires expansion of unique tumor-infiltrating lymphocyte (TIL) cultures from single-cell suspensions processed from melanoma biopsies. Strategies which increase the expansion and reliability of TIL generation from tumor digests are necessary to improve access to TIL therapy. Previous studies have evaluated artificial antigen presenting cells for their antigen-specific and costimulatory properties. We investigated engineered cells for costimulatory enhancement (ECCE) consisting of K562 cells that express 4-1BBL in the absence of artificial antigen stimulation. ECCE accelerated TIL expansion and significantly improved TIL numbers (P=0.001) from single-cell melanoma suspensions. TIL generated with ECCE contain significantly more CD8CD62L and CD8CD27 T cells then comparable interleukin-2-expanded TIL and maintained antitumor reactivity. Moreover, ECCE improved TIL expansion from nonmelanoma-cell suspensions similar to that seen with melanoma tumors. These data demonstrate that the addition of ECCE to TIL production will enable the treatment of patients that are ineligible using current methods.
采用过继性 T 细胞疗法治疗患者需要从源自黑色素瘤活检的单细胞悬液中扩增独特的肿瘤浸润淋巴细胞（TIL）培养物。需要提高从肿瘤消化物中生成 TIL 的扩增和可靠性的策略，以改善 TIL 治疗的可及性。先前的研究已经评估了人工抗原呈递细胞的抗原特异性和共刺激特性。我们研究了由表达 4-1BBL 的 K562 细胞组成的工程细胞的共刺激增强（ECCE），而没有进行人工抗原刺激。ECCE 加速了 TIL 的扩增，并显著提高了单细胞黑色素瘤悬浮液中 TIL 的数量（P=0.001）。与用白细胞介素-2 扩增的 TIL 相比，用 ECCE 生成的 TIL 含有更多的 CD8CD62L 和 CD8CD27 T 细胞，并保持抗肿瘤反应性。此外，ECCE 改善了非黑色素瘤细胞悬浮液中 TIL 的扩增，类似于黑色素瘤肿瘤中的情况。这些数据表明，将 ECCE 添加到 TIL 生产中将能够治疗目前方法不合格的患者。
