TY - JOUR
T1 - Potential clinical application of tumor-infiltrating lymphocyte therapy for ovarian epithelial cancer prior or post-resistance to chemotherapy
AU - Sakellariou-Thompson, Donastas
AU - Forget, Marie Andrée
AU - Hinchcliff, Emily
AU - Celestino, Joseph
AU - Hwu, Patrick
AU - Jazaeri, Amir A.
AU - Haymaker, Cara
AU - Bernatchez, Chantale
N1 - Funding Information:
This research was supported in part by the MD Anderson Cancer Center Support Grant (P30 CA016672), a T32 training grant for gynecologic oncology (CA101642), the MD Anderson Ovarian Cancer Moon Shot program, and an MD Anderson Institutional Research Grant (Amir A. Jazaeri). We also acknowledge the support of the Flow Cytometry and Cellular Imaging, Research Histology, and Characterized Cell Line cores which are also supported by the support grant (P30 CA016672).
Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
KW - Adoptive cell therapy
KW - Ovarian cancer
KW - TIL therapy
KW - Tumor-infiltrating lymphocytes
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U2 - 10.1007/s00262-019-02402-z
DO - 10.1007/s00262-019-02402-z
M3 - Article
C2 - 31602489
AN - SCOPUS:85073981847
SN - 0340-7004
VL - 68
SP - 1747
EP - 1757
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 11
ER -