Table 2.
Clinical efficacy of RNA-based DC trials.
| Study Reference | # Pts | Disease and Combination Treatment | DC Culturing | Maturation | RNA-Transfection | Clinical Response |
|---|---|---|---|---|---|---|
| [35] | 6 | Melanoma, stage IV | Standard (Clinimacs) | TNFα + PGE2 | EP with aT-RNA | No objective clinical response |
| [44] | 11 | Melanoma stage III | Standard | MCM + TNFα + PGE2 | EP with gp100 or tyrosinase mRNA | No information regarding clinical responses, vaccine-related CTL-responses in 7 pts |
| [41] | 35 | Melanoma, m | Standard (6 days) | TriMix- mRNA | EP with MAGE-A3, -C2, tyrosinase, gp100 mRNA | Of 20 pts with measurable disease 11 pts SD, 9 pts PD. Of 15 pts without measurable disease 9 showed relapse. |
| [45] | 45 | Melanoma stage III and IV, m | Standard (5–7 days) | MCM + PGE2 + TNFα | EP with gp100 and tyrosinase mRNA | Stage III: median PFS 34.3 months; mOS not reached. Stage IV (19 pts): 6 SD, 1 PR, 12 PD; mOS 24.1 months (patients with positive immunomonitoring) |
| [49] | 12 | Melanoma, m | Standard (5 days) | MCMM | EP with gp100, MelanA, tyrosinase, and MAGE-A3 mRNA +/− IP siRNA | 1 pt PR 1 pt CR mOS 35 months |
| [42] | 15 | Melanoma | Standard (6 days) | TriMix-mRNA | EP with gp100-, tyrosinase-, MAGE-A3-, and -C2-DC-Lamp mRNA | 2 pts with CR 2 pts with PR 4 pts with SD |
| [46] | 15 | Melanoma | Standard | TriMix-mRNA | EP with gp100 and tyrosinase mRNA | Mpfs = 15.14 months mOS = 23.36 months 1 pt = not evaluable 7 pts with PD 2 pts with SD 1 pt with MR 3 pts with no evidence of disease |
| [40] | 30 | Melanoma (adjuvant) | Standard (6 days) | TriMix or polyIC + CD40L-mRNA | EP with MAGE-A1-, -A3-, -C2-, tyrosinase-, melanA-, and gp100-DC-Lamp RNA | mRFS = 22 months St IIIB/C = 18 months, OS = not reached St III = 36 months; OS = 6.2 years St IIB IIC II 24–27 months; OS = 5.3 years mOS = not reached |
| [47] | 28 | Melanoma stage III and IV | Standard | TLR-agonists from conventional vaccines | EP with gp100 and tyrosinase mRNA | 4 pts with SD |
| [37] | 31 | Advanced melanoma | Standard | MCMM | EP with aT-RNA | 1 pt with PR 3 pts with SD OS 10 months |
| [50] | 22 | Malignant melanoma Cyclophosphamide | Standard | ns | EP with hTERT, survivin, p53 mRNA | 9 pts with SD mPFS 3.1 months mOS 10.4 months |
| [43] | 39 | Pretreated advanced melanoma Ipilimumab | Standard (6 days) | TriMix-mRNA | EP with MAGE-A3-, -C2-, tyrosinase-, and gp100-DC-LAMP mRNA | 8 pts with CR 7 pts with PR 6 pts with SD mPFS 27 weeks mOS 59 weeks |
| [48] | 23 | Uveal melanoma | Standard | ns | EP with gp100 and tyrosinase mRNA | mDFS 34.5 months mOS 51.8 months |
| [60] | 1 | Advanced serous papillary ovarian cancer stage IIIc | Standard | MCMM | EP with folatR mRNA | 1 pt PR |
| [62] | 2 | Ovarian cancer | Standard (6 days) | TNFα + IL1ß | EP with WT1 mRNA | Patients with ovarian carcinosarcoma showed OS of 70 months (vs 15.5 months in historical controls). |
| [63] | 6 | Uterine cancer | Standard (6 days) | TNFα + IL1ß | EP with WT1 mRNA | OS of 10 to 11 months compared to 2–5 months historical controls |
| [31] | 10 | Renal cell carcinoma, stage III or IV | Standard | No | co-incubation with aT-RNA | 7 pts SD/slow progression |
| [34] | 11 | Renal cell cancer, m (10 pts), ovarial carcinoma (1pt) Ontak® | Standard | MCMM | EP with aT-RNA | Increase in tumor-specific CTL, no information on clinical responses |
| [52] | 28 | Renal cell cancer cytokine-induced killer cells | Standard (4 days) | TNFα | EP with MUC-1 and survivin mRNA | 4 pts with CR: 2 > 10 months; 2 > 15 months 7 pts with PR (6–21 months) 10 pts with SD (5–21 months) 6 pts with PD/1 death |
| [36] | 21 | Renal cell cancer sunitinib | Standard | TNFα + PGE2 + IFNγ + CD40L-mRNA | EP with aT-RNA | 5 pts with PR 8 pts with SD 13 pts with PR + SD 8 pts with PD Median OS:30.2 months |
| [56] | 13 | Prostate cancer, m | Standard | No | co-incubation with PSA mRNA | 1 pt decrease of PSA level, 5 pts reduction PSA log slope, 3 pts transient elimination of tumor cells in peripheral blood |
| [39] | 19 | Prostate cancer, androgen resistant | Standard | MCMM | EP with allogeneic tumor RNA (3 human cancer cell lines) | 11 pts SD (PSA) 13 pts decreased log slope PSA |
| [57] | 20 | Prostate cancer, m | Standard | MCMM | EP with hTERT mRNA +/− LAMP | No objective clinical response increase in hTERT-specific CTL and molecular clearence of circulating micrometastases |
| [59] | 21 | Castration-resistant prostate cancer docetaxel | Standard | ns | EP with PSA, PAP, survivin, hTERT mRNA | mPFS 5.5 months |
| [32] | 7 | Pediatric brain tumors | Standard | No | co-incubation with aT-RNA | 0 pt CR, 1 pt PR, 2 pts SD |
| [33] | 8 | Pediatric neuroblastoma stage IV | Standard | No | co-incubation with aT-RNA | No objective clinical response |
| [38] | 7 | Glioblastoma | Standard (5 days) | MCMM | EP with aT-RNA | Median PFS of 694 days vs. 236 days in historical controls Median OS of 759 days vs. 585 days in historical controls |
| [66] | 12 | Glioblastoma injection site preconditioned with tetanus toxoid | Standard | MCMM | EP with CMV pp65 mRNA | mPFS of 10.8 months; mOS 18.5 months |
| [69] | 11 | Glioblastoma temozolimide DCs mixed with GM-CSF | Standard from CD34+ | ns | EP with CMV pp65 mRNA | mPFS 25.3 months mOS 41.1 months |
| [70] | 9 | Glioblastoma adoptive T-cell transfer | Standard | MCMM | EP with CMV pp65 mRNA | increase in polyfunctinal pp65-specific T cells |
| [53] | 3 | Pancreatic adenocarcinoma, CEA expressing | Standard | No | co-incubation with CEA mRNA | 3 pts SD |
| [65] | 42 | Pancreatic cancer cytotoxic lymphocytes gemcitabine | Standard (6 days) | TNFα | EP with MUC-1 mRNA | 1 pt with CR, 3 pts with PR, 22 pts with SD16 pts with PD mOS 13.9 months 1-year survival rate 51.1% |
| [54] | 37 | CEA expressing cancer, m (24 tumor bearing, 13 tumor free) | Standard | No | co-incubation with CEA mRNA | 1 pt CR, 2 pts PR, 2 pts SD |
| [29] | 15 | Colorectal cancer, m | Standard (including FCS) | No | co-incubation with aT-RNA | No objective clinical response |
| [55] | 5 | Colorectal cancer, m | Standard | MCMM | EP with CEA mRNA | Median progression free survival of 26 months |
| [30] | 1 | Adenocarcinoma, m | Standard | TNFα | lipofection of aT-RNA | No objective clinical response |
| [51] | 12 | Multiple myeloma | Standard | MCMM | EP with BCMA, MAGE3, and survivin mRNA | After 25 months 10 of 12 pts still alive with 5 pts having SD, 5 pts having PD |
| [58] | 21 | AML | ns | ns | EP with hTERT mRNA, +/− LAMP | “vaccination with hTERT-DCs may be associated with favorable recurrence-free survival” |
| [64] | 30 | AML | Standard (6 days) | TNFα+ PGE2 | EP with WT1 mRNA +/− DC-lamp | 9 pts with molecular remission 4 pts with SD relapse reduction rate of 25% |
| [68] | 7 | 4 healthy volunteers, 3 HSCT recipients | Standard (6 days clinimacs) | TNFα, PGE2 | EP with CMV pp65 mRNA | No survival data (vaccination to induce CMV cellular response) |
| [67] | 12 | HCV-related hepato-carcinoma | Standard | TNFα | EP with HSP70 mRNA | 2 pts with CR (min. 33 and 44 months) |
| [72] | 10 | HIV infection | Standard | TNFα + IFNγ+ PGE2 + CD40L mRNA | EP with Gag, Vpr, Rev, and Nef mRNA | 7 pts HIV-specific proliferative immune response |
| [74] | 17 | HIV infection | Standard (6 days) | MCMM | EP with Tat-, Rev-, or Nef-DC-Lamp mRNA | Vaccine-specific immune response |
| [75] | 6 | HIV infection | Standard (clinimacs) | TNFα + PGE2 | EP with Gag-DC-Lamp or Tat-Rev-Nef-DC-Lamp mRNA | Vaccine-specific immune response |
| [71] | 10 | HIV infection | Standard (5 days) | MCMM | EP with Gag and Nef mRNA | increased but short-lived CD4-responses against HIV gag and nef |
| [73] | 35 | HIV infection | Standard | TNFa + IFNγ + PGE2 + CD40L-mRNA | EP with Gag, Vpr, Rev, and Nef mRNA | none |
m: metastatic, pt(s): patient(s), ns: not specified, St.: stage, EP: electroporation, IP: immunoproteasome, (m)OS: (median) overall survival, (m)RFS: (median) relapse free survival; (m)PFS: (median) progression free survival, CR: complete response, PR: partial response, SD: stable disease, PD: progressive disease, HSCT: haematopoietic stem cell transplantation, MCM: monocyte-conditioned medium, MCMM = MCM-mimic (TNFα, IL-1, IL-6, PGE2), aT-RNA: autologous tumor RNA, aTSC-RNA: autologous tumor stem cell RNA, AML: acute myeloid leukemia, MAGE: melanoma-associated antigen, Lamp: lysosome-associated membrane protein, hTERT: human telomerase reverse transcriptase, BCMA: B-cell maturation antigen, MUC1: mucin 1, CEA: carcinoembryonic antigen, PSA: prostate-specific antigen, PAP: prostatic acid phosphatase, WT1: Wilms Tumor 1, CMV: cytomegalovirus, HSP70: heat-shock protein 70, Gag: HIV group-specific antigen, Vpr: HIV viral protein R, Rev: HIV reverse transcriptase, Nef: HIV negative regulatory factor, Tat: HIV trans-activator of transcription, ns: not specified. Standard = Monocytes cultured in GM-CSF and IL-4 (default = 7 days).