Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center (UT MDACC), Unit 904, 7455 Fannin, Houston, TX, 77054, USA.
Department of Gynecologic Oncology and Reproductive Medicine, UTMDACC, Houston, TX, USA.
Cancer Immunol Immunother. 2019 Nov;68(11):1747-1757. doi: 10.1007/s00262-019-02402-z. Epub 2019 Oct 10.
Immunotherapy has become a powerful treatment option for several solid tumor types. The presence of tumor-infiltrating lymphocytes (TIL) is correlated with better prognosis in ovarian cancer, pointing at the possibility to benefit from harnessing their anti-tumor activity. This preclinical study explores the feasibility of adoptive cell therapy (ACT) with TIL using an improved culture method.
TIL from high-grade serous ovarian cancer were cultured using a combination of IL-2 with agonistic antibodies targeting 4-1BB and CD3. The cells were phenotyped using flow cytometry in the fresh tissue and after expansion. Tumor reactivity was assessed against HLA-matched ovarian cancer cell lines via IFN-γ ELISPOT.
Ovarian cancer is highly infiltrated with CD8 TIL that are preferentially and robustly expanded with the addition of the agonistic antibodies. With a 95% success rate, the TIL are grown to ≥ 100 × 10 cells in 2-3 weeks without over differentiation. In addition, the CD8 TIL grown with this method showed HLA-restricted tumor recognition.
These results indicate the viability of TIL ACT for refractory ovarian cancer by allowing for the large expansion of anti-tumor TIL in a short time and consistent manner.
免疫疗法已成为多种实体肿瘤类型的有力治疗选择。肿瘤浸润淋巴细胞（TIL）的存在与卵巢癌的预后较好相关，这表明有可能受益于利用其抗肿瘤活性。这项临床前研究探索了使用改良培养方法进行 TIL 过继细胞疗法（ACT）的可行性。
使用 IL-2 与针对 4-1BB 和 CD3 的激动性抗体联合培养来自高级别浆液性卵巢癌的 TIL。使用流式细胞术在新鲜组织和扩增后对细胞进行表型分析。通过 IFN-γ ELISPOT 评估针对 HLA 匹配的卵巢癌细胞系的肿瘤反应性。
卵巢癌高度浸润 CD8 TIL，通过添加激动性抗体可优先且强烈扩增。以 95%的成功率，TIL 在 2-3 周内可生长至≥100×10 个细胞，而不会过度分化。此外，用这种方法培养的 CD8 TIL 表现出 HLA 限制的肿瘤识别。
这些结果表明通过允许在短时间内以一致的方式大量扩增抗肿瘤 TIL，TIL ACT 对于难治性卵巢癌是可行的。
