Potential clinical application of tumor-infiltrating lymphocyte therapy for ovarian epithelial cancer prior or post-resistance to chemotherapy.

Autor: Sakellariou-Thompson D; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center (UT MDACC), Unit 904, 7455 Fannin, Houston, TX, 77054, USA., Forget MA; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center (UT MDACC), Unit 904, 7455 Fannin, Houston, TX, 77054, USA., Hinchcliff E; Department of Gynecologic Oncology and Reproductive Medicine, UTMDACC, Houston, TX, USA., Celestino J; Department of Gynecologic Oncology and Reproductive Medicine, UTMDACC, Houston, TX, USA., Hwu P; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center (UT MDACC), Unit 904, 7455 Fannin, Houston, TX, 77054, USA., Jazaeri AA; Department of Gynecologic Oncology and Reproductive Medicine, UTMDACC, Houston, TX, USA., Haymaker C; Department of Translational Molecular Pathology, UT MDACC, Unit 2951, 2130 W. Holcombe Blvd., Houston, TX, 77030, USA. chaymaker@mdanderson.org., Bernatchez C; 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.; Department of Translational Molecular Pathology, UT MDACC, Unit 2951, 2130 W. Holcombe Blvd., Houston, TX, 77030, USA. cbernatchez@mdanderson.org.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2019 Nov; Vol. 68 (11), pp. 1747-1757. Date of Electronic Publication: 2019 Oct 10.
DOI: 10.1007/s00262-019-02402-z
Abstrakt: 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 × 10 6 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.
Databáze: MEDLINE
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