Table 2.
Samples of clinical studies of cell-based immunotherapy in epithelial ovarian cancer
| Authors | No. of patients (n) | Intervention | Outcome | Comments |
|---|---|---|---|---|
| Kershaw et al.43 | 8 in cohort 1; 6 in cohort 2 | T cells with reactivity against the ovarian cancer–associated antigen α-folate receptor (FR) were generated from autologous T cells with a chimeric gene incorporating an anti-FR single-chain antibody linked to the signaling domain of the Fc receptor γ chain. Eight patients in cohort 1 received a dose escalation of T cells in combination with high-dose interleukin-2, and six patients in cohort 2 received dual-specific T cells (reactive with both FR and allogeneic cells) followed by immunization with allogeneic peripheral blood mononuclear cells | no response was observed. 111In-labeled adoptively transferred T cells in cohort 1 did not show any tumor localization except in one patient where some signals were detected in the peritoneal deposit | phase 1 study in which all 14 patients had metastatic disease and had undergone surgical debulking and combination chemotherapy |
| Haas et al.44 | 15 patients in total: 6 in cohort 1; 3 each in cohorts 2, 3, and 4 | CAR was directed at mesothelin and contained CD3z and 4-1BB in the lentiviral construct. Cohorts 1 and 2 patients received 1–3 × 107 m2 and cohorts 3 and 4 patients received 1–3 × 108/m2 CAR-T cells. Patients in cohorts 2 and 4 also received lymphodepletion with cyclophosphamide, 1.5 g/m2 3 ± 1 day prior to CAR-T infusion | stable disease was observed in 11/15 patients on day 28 | phase 1 study that included 5 patients each, with ovarian cancer, malignant pleural mesothelioma, and pancreatic cancer |
| Aoki et al.39 | 17 patients with advanced/recurrent EOC | 7 patients received TILs following one dose of cyclophosphamide (group A) and 10 received alternating cisplatin-containing regimen and TILs (group B) | 1 CR and 4 PR in group A, and 7 CR and 2 PR in group B | responses in both primary and metastatic lesions lasted 3–5 months in group A |
| Fujita et al.40 | 13 | all patients were treated in the adjuvant setting after surgical debulking and cisplatin regimen. Each received >1 × 109 TILs | 3-year DFS was 81.2% and OS 100% | compared with a control group of 11 patients, DFS and OS were significantly prolonged |
| Freedman et al.41 | 8 patients with advanced EOC refractory to platinum-based chemotherapy | all patients received 1010–1011 TILs intraperitoneally and recombinant interleukin-2. One patient received two doses of TILs | no measurable response was observed in any of the patients | pilot study to evaluate feasibility and clinical response of intraperitoneal TILs |
| Liu et al.45 | 92 | all patients were treated in the adjuvant setting following surgical debulking and 6–8 cycles of carboplatin/paclitaxel; 46 patients were treated with monthly CIK cells and 46 in the control group with observation only | PFS was 37.7 months in the treatment group compared with 22.2 months in the control group (p = 0.004). OS was not improved | paired study of monthly maintenance CIK cells |
| Pedersen et al.42 | 6 | all patients had platinum-resistant progressive metastatic EOC. They all received TILs followed by rIL-2 | 4 patients showed stable disease for 3 months and 2 for 5 months | high number of infused TILs expressed LAG-3 and PD-1 |
| Wright et al.46 | 7 | all patients had recurrent EOC confined to the peritoneal cavity. They received peripheral blood lymphocytes stimulated with MUC1 intraperitoneally | 1 patient attained CR | no significant reduction in serum CA125 |
CR, complete response; PR, partial response; DFS, disease-free survival; OS, overall survival; PFS, progression-free survival; TILs, tumor-infiltrating lymphocytes; CIK, cytokine-induced killer; rIL-2, recombinant interleukin-2; MUC1, Mucin 1; LAG-3, lymphocyte activation gene 3; PD-1, programmed cell death protein 1; CA125, carbohydrate antigen 125.