Departments of Melanoma Medical Oncology.
Head and Neck Surgery, The University of Texas MD Anderson Cancer Center (MDACC), Houston, TX.
J Immunother. 2018 Nov/Dec;41(9):399-405. doi: 10.1097/CJI.0000000000000230.
In this study, we address one of the major critiques for tumor-infiltrating lymphocyte (TIL) therapy-the time needed for proper expansion of a suitable product. We postulated that T-cell receptor activation in the first phase of expansion combined with an agonistic stimulation of CD137/4-1BB and interleukin-2 would favor preferential expansion of CD8 TIL. Indeed, this novel 3-signal approach for optimal T-cell activation resulted in faster and more consistent expansion of CD8CD3 TIL. This new method allowed for successful expansion of TIL from cutaneous and uveal melanoma tumors in 100% of the cultures in <3 weeks. Finally, providing the 3 signals attributed to optimal T-cell activation led to expansion of TIL capable of recognizing their tumor counterpart in cutaneous and uveal melanoma. This new methodology for the initial phase of TIL expansion brings a new opportunity for translation of TIL therapy in challenging malignancies such as uveal melanoma.
在这项研究中，我们解决了肿瘤浸润淋巴细胞 (TIL) 治疗的主要批评之一——适当产品扩展所需的时间。我们假设在扩展的第一阶段激活 T 细胞受体，同时激动性刺激 CD137/4-1BB 和白细胞介素-2，将有利于优先扩增 CD8 TIL。事实上，这种新型的 3 信号方法用于最佳 T 细胞激活，导致更快和更一致的 CD8CD3 TIL 扩增。这种新方法允许在 <3 周内从皮肤和葡萄膜黑色素瘤肿瘤成功扩增 TIL。最后，提供归因于最佳 T 细胞激活的 3 个信号导致扩增能够识别其在皮肤和葡萄膜黑色素瘤中的肿瘤对应物的 TIL。这种用于 TIL 扩展初始阶段的新方法为 TIL 治疗在葡萄膜黑色素瘤等具有挑战性的恶性肿瘤中的转化带来了新的机会。
