Adoptive T Cell Therapy in Patients With Recurrent Ovarian Cancer
Status:
Recruiting
Trial end date:
2021-12-01
Target enrollment:
Participant gender:
Summary
The clinical benefit of standard treatment for patients with epithelial ovarian cancer (EOC)
are poor. Ovarian cancer is a highly immunogenic tumor and good survival is tightly linked to
the presence of tumor-infiltrating CD8+ T cells and the absence of immunosuppressive immune
cells. This clear correlation between T cell infiltration and disease progression suggests
that EOC may be sensitive to adoptive cell therapy by infusion of ex-vivo expanded autologous
Tumor Infiltrating Lymphocytes (TIL) provided that immune suppression is reduced.
Carboplatin+paclitaxel chemotherapy is directly killing tumor cells but was also shown to
alleviate immunosuppression for 2 weeks coinciding with enhanced T-cell immunity, potentially
creating a window of opportunity for T-cell based immunotherapy.
In addition, there is evidence that interferon alpha (IFNα) not only may work as a low toxic
preconditioning regimens that creates the space required for the infused TIL but that it also
supports the TIL by sustaining their persistence and indirectly their function, by
upregulation of HLA class I on tumor cells and decreasing the numbers of regulatory T cells.
Based on this we hypothesize that a synergistic clinical effect may be obtained when adoptive
cell therapy with autologous TIL is administered during treatment with chemotherapy and IFNα.
The feasibility and safety of TIL administration is studied in the window of opportunity
created by carboplatin-paclitaxel chemotherapy with or without interferon alpha (IFNα).
Furthermore, exploratory studies will be performed to analyze and confirm the proposed
underlying mechanisms.
Tumor material for TIL production will be collected during first line debulking surgery in
case of FIGO stage IIIC/IV disease (pre-OVACURE) or in case of recurrent platinum sensitive
disease an extra biopsy can be planned (OVACURE).