Adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TILs) is based on infusion of activated and expanded cells isolated from autologous tumor tissue and has primarily been used with success for treatment of malignant melanoma with clinical effect in approximately 50% of patients including 20% obtaining a complete response. Recent studies suggest that TIL based ACT can potentially be used with success in other cancers, including ovarian cancer (OC). The age-standardized incidence of OC in Europe is 13 per 100.000 and it is the 5th leading cause of cancer death among women. If inoperable, the treatment is a combination of chemotherapy. Recurrent disease has a poor prognosis. The primary aim of this study is to assess feasibility and tolerability of T cell therapy for OC. Secondarily, to describe objective response using RECIST 1.1 and clarify if the treatment can induce a measurable immune response against tumor cells.
Patients with progressive/recurrent OC and histologically verified serous adenocarcinoma are potential candidates. Surgery is performed with removal of tumor tissue for T cell expansion. Stem cells are then harvested for potential use if patients are having difficulties recovering from lymphodepleting chemotherapy before T cell therapy. The treatment consists of high-dose chemotherapy (60 mg/kg cyclophosphamide for 2 days and 25 mg/m2 fludarabine for 5 days) followed by T cell administration and subsequent high-dose decrescendo interleukin-2 for up to 5 days. Patients are evaluated for up to 5 years or until progression.
Five patients are presently included and 3 have received T cell therapy. One had a partial metabolic response, stable disease (SD) with nearly 20% tumor regression and > 50% reduction of CA-125 at 6 weeks, but progressive disease (PD) at 12 weeks. The second had SD at 6 weeks with a small decrease in CA-125, but PD at 12 weeks. The third had SD at 6 weeks with a 25% drop in CA-125 and awaits 2nd evaluation. Only expected and manageable toxicities have been observed and all patients recovered without the need of stem cell support. Immune analyses are pending.
So far, T cell therapy for patients with advanced OC seems to be manageable and tolerable.
Clinical trial identification
Clinicaltrials.gov ID: NCT02482090
Legal entity responsible for the study
Center for Cancer Immune Therapy
Center for Cancer Immune Therapy University of Copenhagen Kræftens Bekæmpelse OvaCure
All authors have declared no conflicts of interest.