DCs (peptide-pulsed) |
HER-2/neu or MUC1-derived peptide | Phase 1/2 study in heavily pretreated metastatic breast and ovarian cancer | 10 (3) | 1 SD over 8 months
1 SD over 8 weeks | Brossart et al., 2000 [3] |
Mannan-MUC1 | Phase 1 study in MUC1+ adenocarcinoma | 11 (1) | 1 SD | Loveland et al., 2006 [4] |
mRNA-encoded FR-α | Pilot study in a patient with recurrent ovarian cancer | 1 | 1 PR | Hernando et al., 2007 [11] |
Lapuleucel-T, pulsed with BA7072, a recombinant fusion protein of HER-2/neu sequences linked to GM-CSF | Phase 1 study in HER-2/neu expressing metastatic breast, ovarian, and colorectal cancer | 18 (4) | 2 SD over 15.7–18.3 months | Peethambaram et al., 2009 [5] |
HER-2/neu, hTERT, and PADRE | Phase 1/2 study in advanced ovarian cancer after first recurrence, randomized to receive low-dose cyclophosphamide prior to vaccination | 11 | 6 NED at 36 months
3-yr PFS 80%
3-yr OS 100% | Chu et al., 2012 [7] |
WT1 mRNA-loaded DC | Phase 1 study in epithelial ovarian carcinoma (OC) and ovarian carcinosarcoma (OCS) | 2 | OS 19 (OCS) and 12 (OC) months after drug cessation | Coosemans et al., 2013 [12] |
Combinations of WT1, MUC1, and CA125 | Retrospective study including patients with recurrent ovarian cancer | 56 | 1-yr OS 87%
2-yr OS 65%
2 PR, 14 SD
DCR 29%
ORR 3.6% | Kobayashi et al., 2014 [6] |
CVac, MUC-1 targeted DC | Phase 2b study (CAN-003 trial) in epithelial ovarian cancer as maintenance therapy | 56 | PFS 13 months CVac vs. 9 mo standard of care (HR 0.72, p = 0.33)
Median OS 25.5 months with standard therapy vs. not yet reached with CVac (HR 0.17; 95% CI 0.02–1.44; p = 0.07) | Gray et al., 2016 [8] |
Neoantigen peptides | Pilot study in a patient with advance ovarian cancer | 1 | CA-125 decreased from 4470 to 1303 U/mL. Patient expired approx. 1 year from treatment start | Morisaki et al., 2020 [9] |
DCs (whole tumor lysate-pulsed) |
Pulsed with KLH and autologous tumor cell lysate | Phase 1 study in advanced gynecologic malignancies | 8 (6) | PFI 25.5 months | Hernando et al., 2002 [13] |
Pulsed with autologous tumor cell lysate supernatant | Pilot study in advanced ovarian cancer where patients were treated with metronomic cyclophosphamide and bevacizumab followed by vaccination | 6 | 2 PR
2 SD | Kandalaft et al., 2013 [14] |
DC pulsed with autologous hypochlorous acid-oxidized ov ca lysate | Pilot study in advanced ovarian cancer | 5 | 2 SD
2 PD
1 mixed response | Chiang et al., 2013 [15] |
APCEDEN, whole-tumor lysate pulsed DCs | Phase 2 study in refractory solid malignancies | 51 (7) | 1 PR
2 SD | Bapsy et al., 2014 [16] |
Pulsed with oxidized autologous whole-tumor cell lysate | Pilot study in recurrent ovarian cancer using autologous vaccine with bevacizumab and cyclophosphamide | 25 | 2 PR
14 SD | Tanyi et al., 2018 [17] |
CTA |
ESO157–170 | Phase 1 study in NY-ESO-1-expressing ovarian cancers | 18 | PFS 19.0 months | Odunsi et al., 2007 [18] |
NY-ESO-1b peptide and Montanide ISA-51 | Phase 1 study in “high-risk” ovarian cancer | 9 | PFS 13.0 months | Diefenbach et al., 2008 [19] |
Synthetic overlapping long peptide from NY-ESO-1, Montanide ISA-51, and Poly-ICLC | Phase 1 study in advanced ovarian cancer in 2nd or 3rd remission | 28 | 6 NED
PFS range of 17–46 months | Sabbatini et al., 2012 [20] |
NY-ESO-1, decitabine, and GM-CSF | Phase 1 study in relapsed ovarian cancer receiving doxorubicin as salvage therapy | 12 | 1 PR
5 SD | Odunsi et al., 2014 [21] |
Protein/Peptide |
HER-2/neu and GM-CSF | Phase 1 study in stage III or IV breast or ovarian cancer | 6 (2) | Responses short-lived | Knutson et al., 2002 [22] |
p53-SLP | Phase 2 study in recurrent epithelial ovarian cancer | 20 | 2 SD | Leffers et al., 2009 [23] |
p53-SLP | Long term outcomes of 2009 phase 2 study | 20 | RR 60.0%
Median DSS 44.0 months | Leffers et al., 2012 [24] |
p53-SLP with cyclophosphamide | Phase 2 study in recurrent ovarian cancer | 10 | 2 SD | Vermeij et al., 2011 [25] |
Wildtype p53 vaccine with Montanide and GM-CSF; p53-pulsed DC | Phase 2 study in high recurrence risk ovarian cancer. Two p53 vaccine approaches tested | 13 | Median OS 40.8 and 29.6 months arm A and B, respectively
Median PFS 4.2 and 8.7 months, respectively | Rahma et al., 2012 [26] |
Flt3 ligand | Pilot study in peritoneal carcinomatosis or mesothelioma patients | 15 (9) | No objective responses | Freedman et al., 2003 [27] |
Anti-idiotypic antibody vaccine (ACA125) | Phase 1/2b study in advanced ovarian cancer | 119 | Median OS 19.4 months (range 0.5–56.1 months)
Ab3-positive patients had significantly longer survival time (median 23.4 mo, p < 0.0001) compared with Ab3-negative (median 4.9 mo) | Reinartz et al., 2004 [28] |
Regimen 1: predesignated SART2 or ART4-derived peptide
Regimen 2: peptides to which preexisting CTL precursor | Two regimens with different peptide vaccine regimens in recurrent gynecologic cancers | Regimen 1: 4 (2)
Regimen 2: 10 (3) | Regimen 1: 0 response
Regimen 2: 1 SD | Tsuda et al., 2004 [29] |
Multipeptide vaccine with Montanide ISA-51 and GM-CSF | Phase 1 study in HLA-A1+, HLA-A2+, or HLA-A3+ epithelial ovarian, fallopian tube, or primary peritoneal carcinoma | 9 | DFS 19 months in 1 patient | Chianese-Bullock et al., 2008 [30] |
WT1 peptide + Montanide ISA51 | Phase 1 study in gynecological cancer patients with WT1/HLA-A *2402 positive tumors | 12 (6) | 1 SD | Ohno et al., 2009 [31] |
WT1 peptide vaccine | Phase 2 study in progressive gynecologic cancers | 40 (24) | 10 SD
OS HR 1.17 (95% CI 0.44–3.14; p = 0.75) | Miyatake et al., 2013 [32] |
Multipeptide vaccine with Montanide ISA-51 and CM-CSF | Phase 1 study in HLA-A2+, stage II to IV epithelial ovaria, tubal, or primary peritoneal carcinoma after 1st or 2nd cytoreductive surgery with a complete clinical response | 15 (8) | Median survival not reached | Morse et al., 2011 [33] |
Personalized peptide vaccine (based on HLA-A types and IgG responses to peptides in pre-vaccinated plasma) with Montanide ISA-51 | Phase 2 study in recurrent or persistent ovarian, fallopian tube, or primary peritoneal carcinoma | 42 | MST in platinum-sensitive vs. platinum-resistant 39.3 vs. 16.2 months, respectively.
MST with monotherapy vs. in combination with chemotherapy in platinum-sensitive (39.3 vs. 32.2 months, respectively) and platinum-resistant (16.8 vs. 16.1 months, respectively) | Kawano et al., 2014 [34] |
Folate receptor alpha with cyclophosphamide priming | Phase 1 study in stage II-IV ovarian cancer and stage II-III breast cancer without evidence of disease | 22 (14) | All patients alive at last follow-up of at least 2 years
Median RFS 528 days in patients in first remission
Median OS not reached for those in second remission | Kalli et al., 2018 [35] |
Polyvalent vaccine-KLH conjugate (including Globo-H-KLH, GM2-KLH,
Tn-MUC1-32mer-KLH, TF-KLH) with adjuvant OPT-821 | GOG 255 – Randomized, double-blinded, phase 2 study in any stage ovarian, fallopian tube, or primary peritoneal carcinoma in 2nd or 3rd complete remission. Patients were randomized to polyvalent vaccine-KLH conjugate + OPT-821 or OPT-821 alone (reference arm) | 171 | KLH + OPT-821 was not superior to OPT-821 alone (HR 0.98; 2-sided 95% CI, 0.71–1.36)
Median OS for KLH + OPT-821 and OPT-821 were 47 and 46 months, respectively. | O’Cearbhaill et al., 2019 [36] |
Recombinant Viral |
Recombinant vaccinia- and fowlpox-NY-ESO-1 | Pilot study in advanced NY-ESO-1-expressing cancers | 35 (1) | DFI 8 months | Jager et al., 2006 [37] |
PANVAC | Pilot study in CEA- or MUC-1-expressing metastatic cancers | 25 (3) | PFS range 2–19 months
OS range 6–21 months | Gulley et al., 2008 [38] |
PANVAC | Pilot study in metastatic ovarian and breast cancer with progressive disease | 26 (14) | Median PFS 2 months (range 1–6 months)
Median OS 15.0 months (range 1.5–57+ months) | Mohebtash, et al., 2011 [39] |
Recombinant vaccinia- and fowlpox-NY-ESO-1 | Two parallel phase 2 studies in NY-ESO-1-expressing epithelial ovarian cancer and melanoma | 47 (22) | Median PFS 21 months (95% CI, 16–29 months)
Median OS 48 months (95% CI, not estimable). | Odunsi et al., 2012 [40] |
Modified Vaccinian Ankara vaccine delivering wildtype human p53 in combination with gemcitabine | Phase 1 study in platinum-resistant recurrent ovarian, fallopian tube, and primary peritoneal carcinoma | 11 | 1 PR
3 SD
Median PFS 3 months (range 0.95–9.2 months) | Hardwick et al., 2018 [41] |
Whole tumor cell |
FANG, an autologous tumor-based vaccine containing a plasmid encoding GM-CSF and a novel bifunctional short hairpin RNA targeting furin convertase | Phase 1 study in advanced cancers | 27 (5) | 3 SD | Senzer et al., 2012 [42] |
Live-attenuated |
ANZ-100, a live-attenuated Listeria vaccine and CRS-207, the live-attenuated Listeria strain expressing human mesothelin | Dual phase 1 study in treatment-refractory mesothelin-expressing cancers (mesothelioma, lung, pancreatic, ovarian) with hepatic metastases | 9 (2) | No clinical responses | Le et al., 2012 [43] |
Carbohydrate-based |
Theratope ® | Phase II/III study in advanced breast and ovarian cancer | 70 (17) | Phase II (40 patients total): 27 patients relapsed (5 ovarian, 22 breast); 23 patients died (5 ovarian, 18 breast)
Phase III (30 patients total): 18 patients relapsed (9 ovarian, 9 breast); 10 patients died (5 ovarian, 5 breast) | Holmberg et al., 2003 [44] |
Lewisy-KLH conjugate with QS-21 adjuvant | Phase I study in recurrent or persistent ovarian, fallopian tube, or primary peritoneal carcinoma following primary therapy and were in complete clinical remission following additional chemotherapy | 25 | Median PFS 6 months
5 patients remained in complete clinical remission at 18 months follow up | Sabbatini et al., 2000 [45] |