Table 1.
Different vaccines in CRC clinical trials.
| Type of Immunotherapy | Status/Country | Route of administration | Clinical Phase | Vaccination Strategy | Combination Therapy | Main Findings | NCT identifier | Ref. |
|---|---|---|---|---|---|---|---|---|
| Tumor cell-based vaccines | Terminated (Business Decision to pursue other indications) United States |
i.d. | II | Vigil™ autologous vaccine that contains rhGM-CSF transgene and a bifunctional shRNA construct to knockdown furin | FOLFOX-6 (Chemotherapy) | -Patients showed no evidence of disease recurrence for over 8 years. -A systemic immune response to vigil therapy was observed. |
NCT01505166 | (20) |
| RNA-pulsed DC vaccine | Completed United State |
i.v. | I/II | dendritic cells are taken from patients then pulsed with CEA RNA then reinjected into the patient’s body | NA | - Administering patients with advanced malignancies with mRNA-loaded DC is both feasible and safe | NCT00003433 | (21) |
| Autologous tumor cell vaccine plus BCG vaccine | United State Netherland |
i.d. | III | adjuvant active specific immunotherapy (ASI) with an autologous tumour cell-BCG vaccine with surgical resection | ASI BCG vaccine |
ASI showed a: -mininal adverse reactions - a significant clinical benefit observed in surgically resected patients with stage II colon cancer |
NA | (22) |
| Autologous tumor lysate with Cytokine-Induced Killer Cells | United state Canada |
i.v. | I/II | DC pulsed with autologous tumor lysate combined with CIK | CIK | -Significantly higher levels of IFN-c and IL-12 - Reduced the risk of post-operative disease progression and improved OS |
NA | (23) |
| Autologous tumor lysate pulsed DC and CD40L | United State completed |
i.n. | NA | Autologous monocyte stimulated with rhuGM-CSF then cultured with tumor cell lysate and then on day 7 with recombinant human CD40L | CD40L | -Among the responders, 63% exhibited a 5-year RFS rate. -The DC vaccine with CD40L did not result in increased immune responses. |
NA | (24) |
| Therapeutic autologous dendritic cells | United State Completed |
s.c. i.d. |
II | Patients undergo leukapheresis to obtain autologous DC loaded with: -vaccinia-CEA-MUC-1-TRICOM (PANVAC-V) dendritic cells Then patients receive autologous -fowlpoxCEA-MUC-1-TRICOM (PANVAC-F) vaccine |
-Falimarev -Inalimarev -Sargramostim |
The Recurrence-free survival (RFS) at 2 years was similar in both arms, namely, (DC/PANVAC and PANVAC/GM-CSF) | NCT00103142 | (25) |
| Therapeutic autologous dendritic cells | United State Completed |
-Denileukin diftitox i.v. -Recombinant fowlpox-CEA (6D)-TRICOM vaccine i.d. s.c. |
I | Patients receive denileukin diftitox IV over at least 15 minutes -vaccine therapy comprising autologous DC infected with recombinant fowlpox-CEA (6D)-TRICOM | -Denileukin diftitox -Recombinant fowlpox-CEA(6D)/TRICOM vaccine |
- Combining Denileukin diftitox with vaccines is safe and effective, with promising results observed in the multiple-dose group, but not in the single-dose group. | NCT00128622 | (26) |
| Mutant ras peptide-based vaccine | United State Completed |
s.c. | II | -Patients received 13-mer mutant ras peptide, spanning aa 5– 17 - 250 µg of DETOX - 25 µg of monophosphoryl lipid A (MPL) |
-DETOX (cell wall skeleton of Mycobacterium phleia) - MPL from Salmonella Minnesota R 595 |
-The vaccine is feasible, safe, and has a positive effect on immune response and overall survival. | NA | (27) |
| Mutated Ras peptide Vaccine | United State Completed |
s.c. | II | Arm 1: Patients receive vaccine and Detox pc with IL-2 -Arm 2: patients received Vaccine admixed with DetoxPC sc and GM-SCF -Arm 3: Patients received vaccine admixed with DetoxPC sc with Il-2 and GM-CSF |
-IL-2 (aldesleukin) -GM-CSF (sargramostim) -DetoxPC |
-Il-2 has a negative effect on the immune response induced by the mutated Ras peptide vaccine. -Highest immune response was seen in Arm 2, where vaccine is combined with GM-CSF. |
NCI97C0141 | (28) |
| messenger ribonucleic acid (mRNA)-based vaccine | United State Terminated (slow accrual) |
i.m. | I/II | Using tumor-infiltrating lymphocytes (TIL) a specific immunogenic mutations expressed in patients' tumor are identified. -The validated and defined neoantigens, predicted neoepitopes, and mutations of driver genes were concatenated into a single mRNA construct |
NA | Safe and induced T cell response against predicted neoantigen. | NCT03480152 | (29) |
| ZYC300 | United State Completed |
i.m. | I | ZYC300 is a DNA plasmid vaccine administered at least 6 and up to 12 doses in alternating lateral quadriceps at 400 µg DNA/dose once every 2 weeks | NA | -Safe and feasible -Unexpectedly, an association between immunity to CYP1B1 and response to salvage therapy was noticed |
NA | (30) |
| Influenza vaccine | Denmark Completed |
i.t. | I/ II | Intratumoral application of an unattenuated influenza vaccine | Curative surgery | -Elevated level of CD8+ T cells infiltration in tumor accompanied by an increase in the transcript expression encoding to cytotoxic activity. - Upregulation of PD-L1 and downregulation of FOXP3. |
NCT04591379 | (31) |
| Ad5-hGCC-PADRE vaccine | United State Completed |
i.m. | I | -GUCY2C residues 1–429 with a C-terminal PADRE epitope cloned into the E1 region of pAd/CMV/V5 obtaining E1- and E3-deleted human serotype 5 adenovirus | Surgically resected stage I/II | -CD8+T cell and antibody response against self-antigen with no detection of CD4+ T cells. | NCT01972737 | (32) |
| AD5 CEA Vaccine | United State Completed |
s.c. | I/II | It is a dose escalating strategy: -Cohort 1: Received 1×109 VP in 0.5 ml subcutaneously (SQ) in the same thigh every 3 weeks for 3 immunizations -Cohort 2: dose of 1×1010 VP in 0.5 ml SQ every 3 weeks for 3 treatments -Cohort 3: dose of 1×1011 in 0.5 ml SQ every 3 weeks for 3 treatments. |
NA | -Safe and effective despite the presence of neutralizing antibody against AD-5. | NCT01147965 | (33) |
| VRP-CEA(6D)/AVX701 | United State Completed |
i.m. | I | 4 x 10EE8 IU intramuscularly every 3 weeks for 4 total immunizations | NA | -Safe and effective T cell response was associated with longer survival in stage IV. -The rate of T cell response and antibody response were higher in stage III. |
NCT01890213 | (34) |
| Ad-sig-hMUC-1/ecdCD40L vector | Singapore Unknown Recruiting last update in October 2016 |
s.c. in preclinical studies | I | -Adenovirus vector encodes for a fusion protein in which the hMUC-1 antigen is connected to CD40L (CD40 ligand) -A dose escalating procedure to determine the maximum dose that can be used with no toxicity |
NA | -Safe and showed low toxicity. -No dose limiting toxicity and MTD wasn’t reached. -Encouraging anti-tumor activity was noticed. |
NCT02140996 | (35, 36) |
| Pexa-Vec | United State | i.v. | I/II | Pexa-Vec is a vaccinia virus with an inactivated thymidine kinase gene that is designed to express hGM-CSF and beta-galactosidase | -Durvalumab -Tremelimumab |
-The vaccine is safe and well tolerated -This combination has demonstrated a potential therapeutic efficacy in pMMR mCRC |
NCT03206073 | (37) |
s.c, subcutaneous; i.d, intradermal; i.v, intravenous; i.n, intranodal; i.m, intramuscular.Not Applicable (NA).