Table 2.
CpG ODN as adjuvant in tumor vaccine trials.
| Trial no. | Type of cancer | Treatment | Route | Phase | Date | Results | Reference |
|---|---|---|---|---|---|---|---|
| NA | Malignant melanoma | 2/Melan-A (100 μg) Montanide® ISA-51 (300 μg), +CpG 7909 (500 μg) n = 16 in 2 group 4× monthly |
SQ | I | NA | CpG group: more rapid (after 2 vs. 4 vaccinations) and 8-fold higher Melan-A-specific CD8 T cell response compared to the non-CpG group (1.15 ± 0.93% vs. 0.13 ± 0.11%, p < 0.01). Response rate was 100% after 4 vaccinations vs. 50% in controls. Clinical response: one patient (12%) remained disease free, one patient SD, 6 patients (75%) PD. | [129] |
| NCT00085189 | Malignant melanoma stage III–IV | NY-ESO-1 (600 μg), Montanide® ISA-51 (3 mL), ±CpG 7909 (2 mg) n = 8 in 3 groups 6× biweekly |
SQ | II | 05/04–09/07 | GpG group: 100% of patients (n = 3) developed NY-ESO-1 specific CD8 T cells which increased 3–10 fold after 6 vaccinations compared to pre-vaccination status. CpG alone (without NY-ESO-1) had no effect. Clinical outcome: 1 (12%) patient had SD for 6 months then progressed as did all other patients. | [140] |
| NCT00306514, 00306566, 00306553 | Malignant melanoma stage II–IV | CYT004-MelQbG10 (1 mg) n = 22 in 4 groups, 6 or 11 vaccinations, (wkly or daily 5x) |
SQ/ID | I/II | 2006 | Significant increase in Ag-specific T cells in 14/22 patients (63%) compared to pre-vaccination status (no differences between groups I-IV). T cells produced TFN-α, IFN-γ and IL-2 and up-regulated expression of surface antigens LAMP-1 and CD107a. Significantly more memory T cells vs. seen patients vaccinated with Melan-A peptide plus IFA (p < 0.05) from study [102]. Clinical response: 7 (31%) patients were free of disease, 1 patient (4%) PR, 11 patients (50%) PD, 1 patient (4%) SD, 2 (9%) patients died. | [42] |
| NCT00651703 | Malignant melanoma stage III–IV | CYT004-MelQbG10, Montanide® ISA-51, Imiquimod 5%, n = 21 in 4 groups 3x wkly, 3x monthly |
SQ/ID/IN | IIa | 04/08–07/10 | 76% of patients responded to MelQbG10 vaccination by a >2 fold increase in Ag-specific T cells. Clinical response: 5 patients (23.8%) had SD, 9 patients (42%) PD, 5 (23%) patients without evidence of disease, 2 (9%) patients died. | [41] |
| NCT00112229 | Malignant melanoma stage III–IV | Melan-A/Mart-1, Tyrosidase (YMD) Montanide® ISA-51 ± CpG 7909 n = 24 in 2 groups monthly |
SQ | I | 04/03–06/12 | CpG group: Melan-A/MART-1 specific T cell frequencies were 10-fold higher (p < 0.01) and produced higher levels of IFN-γ, TNF-α and IL-2 (p < 0.01) compared to non-CpG group. | [115] |
| NA | Malignant melanoma stage III–IV | MART-1, gp100, tytosinase peptides, Montanide® ISA-51, + CpG 7909 (600 μg), GM-CSF (80 μg) n = 22 one group days: 1, 15 (13 cycles) |
SQ | I | 01/09–12/10 | 2 (9.5%) patients had PR, 8 (38%) patients with SD (2–7 months, 50% of them with positive Elispot ≥ 10 spots), 20 (95%) patients had PD in follow up; median PFS 1.87 months, median OS 13.4 months. | [116] |
| NA | Multiple types (melanoma, breast cancer, ovarian cancer, sarcoma) stages I–IV | rNY-ESO-1 (100, 400 μg), Montanide® ISA-51, + CpG 7909 (2.5 mg), n = 18 in 2 groups 4 × 3 week interval |
SQ | NA | NA | 94% of patients developed CD4 T cell responses and 50% CD8 T cell responses. IgG Ab titer of 24 ± 10 in those vaccinated with 100 μg NY-ESO-1; 42 ± 29 in the 400 μg NY-ESO-1 group (preferentially IgG1and IgG3). | [141] |
| NCT00199836 | Multiple types (melanoma, NSCLC, breast cancer, ovarian cancer, sarcoma) stage III–IV | NY-ESO-1b (100 μg), Montanide® ISA-51 (0.5 mL), +CpG 7909 (1 mg) n = 14 one group 4 × 3 week interval |
SQ | I | 09/03–12/05 | Induction of Ag-specific CD8 T cells against NY-ESO-1 in 9 of 14 patients (63%). Clinical response: 2 patients (14%) showed no evidence of disease, 9 patients (64%) had PD, 3 patients (21%) SD. | [142] |
| UMIN 000002771 | Multiple types (colon, pancreatic, rectal, lung, cervical cancer, epitheloid cancer and papilla cancer) | WT-1, GM-CSF (100 μg), Montanide® ISA-51, ±CpG7909 (100 μg) n = 28 in 2 groups 8× weekly |
ID | I | 01/10–11/10 | Clinical response: 60% of patients treated with WT-1 + Montanide® ISA-51 + CpG 7909 showed SD, 40% PD. (WT-1 only: 20% SD, 80% PD; WT1 + GM-CSF:25% SD, 75% PD) | [118] |
| NCT00669292 | Esophageal cancer | URLC10-117 peptide (1 mg), TTK-567 peptide (1 mg), Montanide® ISA-51, + CpG 7909 (0.02, 0.1 mg/kg) n = 9 in 3 groups days: 1, 8, 15, 22 |
SQ | I/II | 11/06–11/09 | Serum levels of IFN-α and 2–5 AS increased with increasing dose of CpG 7909. Increase in IFN-α producing Ag-specific CD8 T cell responses in 33% (TTK-567) or 66% (LY6K-177) of the patients. Clinical response: no partial or complete responses, 33% of patients received 0.02 mg/kg CpG 7909 and 66% of patients received 0.1 mg/kg CpG 7909 showed SD. | [143] |
| NCT00299728 | Prostate cancer | NY-ESO-1 (100 μg), +CpG 7909 (2,5 mg) n = 15 one group 4 × 3 week interval |
ID | I | 03/06–12/06 | 9 patients (60%) had NY-ESO-1 specific CD4 T cells by week 7–28 (mean 14) and 6 patients (40%) had NY-ESO-1 specific CD8 T cell by week 10–28 (mean 14). 2 patients (13%) developed anti-CpG Ab (1:25,000, 1:6,400). Clinical response: 2 patients (13%) showed no evidence of diseases, 8 patients (53%) showed SD and 3 (20%) PD, but no PR or CR was seen after 4 vaccinations. | [128] |