TABLE 2.
Table of completed clinical trials showing promising results for various cancer vaccines in OC. All of these vaccines have been used as a second line of treatment after initial cytoreductive debulking of the primary tumours and chemotherapy.
| Clinical trial ID | Cancer type | Vaccine description | Vaccine type | Therapeutic cargo | Additional intervention | Vaccine delivery route | No. of partici-pants | Phase | Remarks |
|---|---|---|---|---|---|---|---|---|---|
| NCT 01867086 | Stage III/IV OC—Recurrent | Bi-shRNA-furin and GMCSF augmented autologous tumour cell Vaccine | Autologous whole tumour cell vaccine | RNA interference moiety -Bi-shRNA-furin | Drug: Carboplatinum Drug: Carboplatinum and Taxol | ID once every 3 weeks- Max 12 doses or as long as it lasts | 1 | II | All patients were ELISPOT-positive after 12 months (100%). This subject did not complete treatment due to disease progression. After 24 months, subject was not alive. Statistical analysis was not done. This study was terminated |
| NCT 01551745 | Stage III/IV OC- Recurrent/Refractory | Bi-shRNA-furin and GMCSF augmented autologous tumour cell Vaccine | Autologous whole tumour cell vaccine | RNA interference moiety -Bi-shRNA-furin | Drug: Bevacizumab | ID once every 4 weeks -Max 12 doses or as long as it lasts | 5 | II | All patients were ELISPOT positive after 12 months (100%). 1 (20%) patient was alive after 2 years 3/5 showed some serious adverse events like hepatobiliary disorder, infections and infestations and nervous system disorder |
| NCT 01617629 | EOC-stage III/IV | Cvac (MUC 1 Autologous dendritic cells pulsed with recombinant human fusion protein coupled to oxidized Polymannose) | Autologous Dendritic Cell Vaccine (MoDC) | Dendritic cells specific to MUC-1, Manosylated fusion protein | ID injections- every 4 weeks (dose1-3), every 12 weeks (3–6) | 9 | II | Due to the few patients, Overall Survival could not be calculated. All-cause mortality was observed 2/9 patients. Severe adverse events were seen in 22.22% patients with 77.78% patients having other adverse events | |
| NCT 01068509 | EOC- stage III/IV 1st or 2nd remission | Cvac (MUC 1 Autologous dendritic cells pulsed with recombinant human fusion protein coupled to oxidized Polymannose) | Autologous Dendritic Cell Vaccine (MoDC) | Dendritic cells specific to MUC-1, Manosylated fusion protein | ID injections- every 4 weeks for 24 weeks | 63 | IIb | Therapy was safe with only 7 patients. CVac-treated patients had T cells that responded to mucin 1 challenge seen with both CD4+ (helper T cells) and CD8+ (killer T cells). CD8+ cytotoxic T cells showed a greater reactivity than CD4+ T helper cells. Detectable mucin 1-specific T cell response in treated patients as compared to untreated that was measurable over endogenous baseline (unstimulated) suggested a prolonged immune response. Patients with 2nd clinical remission had longer PFS (13 vs. 5 months) and overall survival (>42 vs. 26 months) when compared with unvaccinated patients. 15.38% of the vaccinated patients suffered from serious adverse effects whereas other mild adverse events were observed in 96.15 % of the vaccinated patients | |
| NCT 00091273 | Stage I-IV EOC, Primary Peritoneal Cavity Cancer | Adjuvant vaccine comprising ovarian cancer synthetic peptides, tetanus toxoid helper peptide, and sargramostim (GM-CSF) emulsified in Montanide ISA-51 | Peptide vaccine | Ovarian cancer synthetic peptide | SC and ID in 2 different sites (Day 1, 8, 15, 29, 36 and 43) | 9 | I | Measure of Tumor-antigen-specific Immunity in PBMC by ELISPOT Assay showed response in 8 patients even at 3 months. No serious adverse events or mortality were observed until day 50, however other mild adverse events were observed in all of the patients | |
| NCT 00857545 | Stage I-IV Fallopian Tube Cancer, Stage I-IV OC, Stage III/IV Primary peritoneal cancer In their 2nd/3rd remission | Polyvalent vaccine (including GM2-keyhole limpet hemocyanin [KLH], Globo-H-KLH, Tn-mucin 1 [MUC1]-32mer-KLH, and Thompson Friedreich antigen [TF]-KLH with Saponin-based immunoadjuvant OBI-821 | Conjugate Peptide vaccine | Polyvalent carbohydrate/peptide antigens | SC once in weeks 1, 2, 3, 7, 11, 23, 35, 47, 59, 71, and 83 | 171 | II | <50% of patients were found to have IgM + response to the individual antigens. IgG + responses ranged 7%–45%. MUC1 was the most immunogenic antigen, with 49% and 45% of patients developing a IgM and IgG response, respectively, when comparing the pre- and post-titers. 77% discontinued due to progression, 4% due to toxicity, and 1 due to myeloid dysplastic syndrome (MDS). Lesser adverse events were injection site reactions (82%) and fever (11%). Vaccination with this polyvalent construct with antibody effectors was modestly immunogenic but did not prolong PFS or OS when compared to OPT-821 alone | |
| NCT 00616941 | EOC, Fallopian Tube Cancer, Primary Peritoneal Cancer | Synthetic peptide vaccine encoded by NY-ESO-1 gene in combination with Montanide and polyinosinic-polycytidylic acid - poly-l-lysine carboxymethylcellulose (poly-ICLC) | Peptide vaccine | NY-ESO-1 encoding overlapping peptides- synthetic | SC injection once every 3 weeks for 5 doses | 28 | I | Vaccination induced an integrated immune response (CD4+-100% and CD8+ T 25%–90.9%) post baseline. OLP immunisation alone failed to induce CD4+ T-cell responses; instead, it reduced high-avidity CD4+ T-cell progenitors that had previously identified naturally processed NY-ESO-1 protein. High-avidity NY-ESO-1-specific CD4+ T-cell precursor growth needed OLP emulsification in Montanide. While inhibiting the generation of IL-4 producing Th2 and IL-9 producing Th9 cells, poly-ICLC greatly improved CD4+ Th1 responses | |
| NCT 01223235 | Fallopian Tubes Cancer, OC, Peritoneal Cancer | Polyvalent vaccine-KLH conjugate + OPT-821 | Conjugate Peptide vaccine | Polyvalent carbohydrate/peptide antigens | Drug: Bevacizumab | SC once every week (Doses 1–3), once every 4 weeks (doses 4–6) | 22 | Bevacizumab improved the vaccine’s tolerability. Response was not linked to a higher chance of survival. Increased IL-8 was linked to a considerable improvement in PFS on a two-timepoint analysis. Cytokine levels were not substantially correlated with survival across all timepoint measures. 1 patient experienced toxicity that was dose-limited (grade 4 fever). 2 (10%) patients developed grade 3 hypertension as a result of bevacizumab. 13 (68%) and 16 (84%) of the 19 participants reacted to 3 and 2 antigens, respectively (Globo-H, GM2, TF cluster Tn, MUC-1). Out of the 21 patients, 4 were still living after more than 5 years | |
| NCT 00112957 | Fallopian Tube Cancer, OC, Peritoneal Cavity Cancer | Recombinant vaccinia-NY-ESO-1 (rV-NY-ESO-1) and recombinant fowlpox-NY-ESO-1 (rF-NY-ESO-1) | Recombinant viral nucleic acid vaccine | NY-ESO-1 encoding viral constructs | ID (rV-NY-ESO-1- day 1), SC injections of (rF-NY-ESO-1-once every 4 weeks- 6 doses | 23 | II | 38% of patients were in remission at 1 year. Specific antibody response to the NY-ESO-1 and LAGE-1 measured by ELISA showed increase in response at different timepoints until 12 months when compared to Day 0. Detectable T-cell responses was observed in 90.9% of patients for CD4+ and 45.5% for CD8+ cells. Higher number of patients with release of INF-γ by T Cells (CD4+-75%, CD8+-25%) in response to cancer antigens was observed after vaccination at different timepoints until 12 months 2 patients had to be discontinued because of treatment emergent adverse events with 4 patients facing serious adverse events | |
| NCT 00803569 | Fallopian Tube Cancer, OC, Peritoneal Cavity Cancer | ALVAC(2)-NY-ESO-1(M)/TRICOM vaccine administered with the granulocyte macrophage-colony stimulating factor (GM-CSF) Sargramostim | Recombinant viral vector nucleic acid vaccine | Recombinant genes encoding NYESO-1(M), TRICOM (LFA-3, ICAM-1, B7.1), vvE3L, vvK3L | SC injection once every 4 weeks for 6 doses | 13 | I | The vaccine was well tolerated by all patients with no patients with discontinuation, mortality or any serious treatment related adverse effects. 83.3 % of the patients had no evidence of disease after 24 weeks, 16.7% patients were with progressive disease. Median PFS was observed to be 167.5 days 83.3% and 25% patients were found to have NY-ESO-1 and LAGE-1 antigen positivity post baseline through 24 weeks | |
| NCT 00088413 | Adenocarcinoma, Colorectal Cancer, OC, Breast Cancer | PANVAC-V (Vaccinia) and PANVAC-F (Fowlpox) containing the transgenes for CEA and MUC-1 in Combination With GMCSF | Recombinant viral vector nucleic acid vaccine | Recombinant genes encoding CEA and MUC 1 | SC PANVAC-V-day 1 PANVAC(TM)-F once after every 2 weeks (Dose 2–4) then once every 4 weeks up to 12 doses | 51 | I/II | Side effects were largely limited to mild injection-site reactions. Ovarian cancer: For patients (n = 14), the median time to progression was 2 months (range: 1–6), and the median overall survival was 15.0 months ELISPOT assay of 2 HLA-A2+ ovarian cancer patients who were enrolled in the study for 2 months showed no significant changes without in vitro stimulation, for CEA nor MUC-1. However, after in vitro stimulation with HLA-A2 restricted CEA and MUC-1 peptides for 72 h, 1 of the 2 patients had a 2.7-fold increase in CEA-specific T-cells. Increases in the T effector: Treg ratios were observed in 3 patients | |
| NCT 02179515 | Lung Cancer, Breast Cancer, Prostate Cancer, Tumours (Others), Ovarian Cancer | Modified vaccinia Ankara (MVA)-brachyury-B7-1, ICAM-1 (Intercellular Adhesion Molecule 1), and LFA-3 (lymphocyte function-associated antigen 3) TRICOM vaccine | Recombinant viral vector nucleic acid vaccine | Recombinant gene encoding Brachyury | SC injection once every month for max 6 months | 38 | I | Vaccination with 1 dose was not successful in generating any T-cell response after 85 days, however 35.7% and 60.0% patients developed a response after 2nd and 3rd dose respectively. Single dose did not generate any Anti-Brachyury Antibodies in any patient whereas a 2nd and a 3rd dose generated response in 7.1% and 26.1% patients respectively. Increased production of INF-γ was observed with 2 and 3 doses of the vaccine. Most of the patients suffered from post treatment adverse effects with 2/3, 4/17 and 2/18 patients having serious adverse effects after 1,2 and 3 doses | |
| NCT 00623831 | Melanoma, Sarcoma, Gastrointestinal Stromal Tumor (GIST), Head and Neck Cancer, Transitional Cell Carcinoma, Prostate Cancer, OC, Esophageal Cancer, Breast Cancer | Mixed bacterial vaccine (MBV, Coley’s toxin) | Mixed bacterial vaccine | Heat-inactivated Streptococcus pyogenes and Serratia marcescens Lysate | SC injection twice weekly for 6 weeks | 17 | I | 13 patients were in cohort 1 (dose level 1) and 4 in cohort 2 (dose level 6). After receiving MBV, 11 of them experienced fever (cohort 1). The serum IL-6 levels increased consistently in 10 out of 12 patients, with the maximum levels occurring at the same time as the highest body temperatures. A subgroup of patients displayed rising TNF-, IFN-, and IL1- levels. The partial tumour response in a patient with metastatic bladder cancer was closely linked with MBV-induced fever and raised levels of numerous cytokines |