Donastas Sakellariou-Thompson1, Marie-Andrée Forget1, Emily Hinchcliff2, Joseph Celestino2, Patrick Hwu1, Amir A Jazaeri2, Cara Haymaker3, Chantale Bernatchez4,5. 1. Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center (UT MDACC), Unit 904, 7455 Fannin, Houston, TX, 77054, USA. 2. Department of Gynecologic Oncology and Reproductive Medicine, UTMDACC, Houston, TX, USA. 3. Department of Translational Molecular Pathology, UT MDACC, Unit 2951, 2130 W. Holcombe Blvd., Houston, TX, 77030, USA. chaymaker@mdanderson.org. 4. Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center (UT MDACC), Unit 904, 7455 Fannin, Houston, TX, 77054, USA. cbernatchez@mdanderson.org. 5. Department of Translational Molecular Pathology, UT MDACC, Unit 2951, 2130 W. Holcombe Blvd., Houston, TX, 77030, USA. cbernatchez@mdanderson.org.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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 × 106 cells in 2-3 weeks without over differentiation. In addition, the CD8+ TIL grown with this method showed HLA-restricted tumor recognition. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: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 × 106 cells in 2-3 weeks without over differentiation. In addition, the CD8+ TIL grown with this method showed HLA-restricted tumor recognition. CONCLUSIONS: 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.
Entities:
Keywords:
Adoptive cell therapy; Ovarian cancer; TIL therapy; Tumor-infiltrating lymphocytes
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