Immunotherapy Advances for Epithelial Ovarian Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. EOC Immune Landscape
3. Immunomodulatory Properties of Chemotherapeutic Drugs
4. Monoclonal Antibodies
4.1. CA125
4.2. Folate Receptor Alpha
4.3. EpCAM
4.4. VEGF
4.5. Immune Checkpoint Blocking Antibodies
4.6. CTLA-4
4.7. PD-1/PD-L1
5. Vaccines
5.1. WT1
5.2. MUC1
5.3. NY-ESO-1
5.4. Folate Receptor Alpha
5.5. TP53
5.6. Whole Tumor Cell Lysates
5.7. Neoantigens
6. Cellular Immunotherapy
6.1. TIL Therapy
6.2. TCR Engineered Peripheral Blood Mononuclear Cells (PBMC)
6.3. Chimeric Antigen Receptors
6.3.1. CAR T Cells Targeting MUC1
6.3.2. CAR T Cells Targeting Mesothelin
6.3.3. NKG2D CAR-T Cells
7. Immune Therapy with Oncolytic Viruses
8. Type I Interferon Production Agonists
STING Agonists
9. Conclusions
Funding
Conflicts of Interest
References
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Agent (Target) | Study Phase | Combination | Outcome | Reference | NCT |
---|---|---|---|---|---|
Oregovomab (CA125) | III | No | No significant difference between groups for time to relapse (TTR). Median TTR of 10.3 months [95% CI, 9.7 to 13.0] for oregovomab and 12.9 months [95% CI, 10.1 to 17.4] for placebo (p = 0.29, log-rank test) | [31] | NCT00050375 |
Farletuzumab (FRa) | III | Carboplatin and paclitaxel | No significant difference in progression free survival (PFS). HR 0.99 [95% CI, 0.81 to 1.21] and 0.86 [95% CI, 0.70 to 1.06] for farletuzumab 1.25 mg/kg (p = 0.9025, two-sided log-rank test) and 2.5 mg/kg (p = 0.1521) vs. placebo, respectively. | [32] | NCT00849667 |
Mirvetuximab soravtansine IMGN853 (FRa) | III | No | ORR of 22% (12% for chemo alone) In the high FRa expression group ORR was 24% (10% for chemo alone) | [33] | NCT02631876 |
Catumaxomab (EpCAM) | II/III | Paracentesis | Significant puncture-free survival benefit for catumaxomab + paracentesis vs. paracentesis alone in OC (52 vs. 11 days, respectively, p < 0.0001). No significant survival benefit for catumaxomab + paracentesis vs. paracentesis alone in OC (110 vs. 81 days, respectively, p = 0.1543) | [34] | NCT00836654 |
Bevacizumab (VEGF) | III III | Carboplatin and paclitaxel Olaparib (PARPi) | No survival benefit for bevacizumab vs. chemotherapy. Median OS for stage IV disease: bevacizumab + chemo 42.8 months (32.6 for chemo alone, HR, 0.75; 95% CI, 0.59 to 0.95). Median PFS was 22.1 vs. 16.6 months for olaparib vs. placebo (HR, 0.59; 95% CI, 0.49 to 0.72; p < 0.001). Median PFS for BRCA mutated HRD-positive tumors was 37.2 vs. 21.7 months for olaparib vs. placebo (HR, 0.33; 95% CI, 0.25 to 0.45). Median PFS for non-BRCA HRD-positive tumors was 28.1 vs. 16.6 months for olaparib vs. placebo (HR, 0.43; 95% CI, 0.28 to 0.66). | [35,36] | NCT00262847 NCT02477644 |
AGENT (Target) | Study Phase | Combo | Cohorts | Outcome | PD-L1 | Ref | NCT |
---|---|---|---|---|---|---|---|
Ipilimumab (CTLA-4) | II | None | 38/40 patients did not complete the trial due to toxicity, progression or death | N/A | [59] | NCT01611558 | |
Nivolumab (PD-1) | II | None | A—Low dose—1 mg/kg B—High dose—3 mg/kg 2 patients with CR | A—ORR 10%, DCR 50%, medium PFS 3.5 months, median OS 16.1 months B—ORR 20%, DCR 40%, medium PFS 3.0 months | High expression—16/20, scores +2 to +3 Low expression—4/20, score of +1 | [60] | UMIN000005714 |
Pembrolizumab (PD-1) | II | None | A—received </=2 prior chemotherapy lines for recurrent AOC B—3–5 prior chemotherapy lines | A—ORR 8.1%, median OS 18.7 mo B—ORR 9.9%, median OS 17.6 mo Patients with higher PD-L1 expression had better response in both cohorts | [61] | NCT02674061 | |
Avelumab (PD-L1) | III III | Carboplatin Doxorubicin | A—Carboplatin B—Carboplatin + avelumab 10mg/kg C—Carboplatin + avelumab, w/maintenance A—avelumab 10 mg/kg B—avelumab 10 mg/kg + PLD 40 mg/m2 C—PLD 40 mg/m2 | A—PFS N/A, ORR 27.8% B—PFS 16.8 mo, ORR 25.9% C—PFS 18.1 mo ORR 31.1% A—median PFS 1.9 mo, median OS 11.8, ORR 3.7% B—median PFS 3.7 mo, median OS 15.7 mo, ORR 13.3% C—median PFS 3.5, median OS 13.1 mo, ORR 4.2% ORR 18.5% for PD-L1 pos tumors, 3.4% PD-L1 neg tumors | PD-L1 positive if expression >/=1% of tumor cells or >/=5% immune cells PD-L1 positive if expression >/=1% of tumor cells or >/=5% immune cells | [62,63] | NCT02718417 NCT02580058 |
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Hartnett, E.G.; Knight, J.; Radolec, M.; Buckanovich, R.J.; Edwards, R.P.; Vlad, A.M. Immunotherapy Advances for Epithelial Ovarian Cancer. Cancers 2020, 12, 3733. https://doi.org/10.3390/cancers12123733
Hartnett EG, Knight J, Radolec M, Buckanovich RJ, Edwards RP, Vlad AM. Immunotherapy Advances for Epithelial Ovarian Cancer. Cancers. 2020; 12(12):3733. https://doi.org/10.3390/cancers12123733
Chicago/Turabian StyleHartnett, Erin G., Julia Knight, Mackenzy Radolec, Ronald J. Buckanovich, Robert P. Edwards, and Anda M. Vlad. 2020. "Immunotherapy Advances for Epithelial Ovarian Cancer" Cancers 12, no. 12: 3733. https://doi.org/10.3390/cancers12123733