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Table 2. Trials with therapeutic vaccines
Vaccines Phase Results References
Autologous cancer cells combined with BCG +/- resection III No differences at 7 years [48]
Longer follow up showed benefit in stage II only
Tumour cells incubated with NDV II Reduction in recurrence rate of 61% vs. 87% in [50]
historical
NDV-infected autologous tumour cell vaccine group or control III No differences in OS [51]
group But significant improvement in colon compared
to rectal cancer
Autologous tumour lysate DC vaccines vs. BSC II No benefits in PFS/OS [55]
DC vaccine based on Wilms’ tumour (WT1) class I/II peptides I OS prolongation [56]
Five peptides vaccine/chemotherapy II No benefits in RR/PFS/OS [61]
Seven peptides vaccine/chemotherapy > OS [62]
Fowlpox-CEA(6D)- TRICOM alone and sequentially with I Safe [64]
vaccinia-CEA(6D)- TRICOM with/without GM-CSF in CEA SD as best response
cancers Duration response > 4 m
Chemotherapy/vaccine canarypox virus (ALVAC) expressing II RR 40% [65]
CEA and B7-1 (ALVACCEA/B7-1 But no significant differences
Genetically engineered oncolytic herpes simplex virus I/II TTP 6.4 m [70]
(NV1020)/chemotherapy OS 11.8 m
OS at 1 year 47.2%
Pexa-Vec oncolytic virus/tremelimumab Ib/II
NCT03206073
NDV: Newcastle disease virus; OS: overall survival; GM-CSF: granulocyte macrophage colony-stimulating factor; PFS: progression-free
survival; RR: response rate; DC: dendritic cell; BSC: best supportive care; TTP: time to progression

vaccine was able to stimulate a tumour specific immune response, but no benefits were seen in terms of PFS
(2.7 vs. 2.3 months, P = 0.628) and OS (6.2 months vs. 4.7 months, P = 0.41).

A phase I trial assessed a DC vaccine based on Wilms’ tumour (WT1) class I/II peptides in colon cancer
patients and showed benefit in relation to WT1 expression by immunohistochemistry in tumoral tissue
[56]
and the immunity continued for two years and this was associated with a survival prolongation.

Peptide vaccines
Peptide vaccines can stimulate T cells responses against tumour specific antigens and they could stimulate
tumour specific immune response as well .
[57]
In colon cancer there are several tumour associated antigens that have been used in peptide vaccines.
[60]
CEA , EGFR , mucin 1 , among others.
[58]
[59]
These vaccines have not demonstrated any benefits in survival and some research have been performed to
create vaccines agains several antigens with longer aminoacids. A phase II trial including 96 metastatic colon
cancer patients showed that a peptide vaccine with five peptides is safe if given with chemotherapy . but
[61]
did not show any advantages in response rate, PFS and OS.

Another trial demonstrated that a 7 peptide vaccine combined with chemotherapy in metastatic colon
[62]
cancer produces better OS .

Viral vector vaccines
The pathogenicity of a virus can be used to generate a tumor-specific immune response. Viral vectors can
be engineered to express any antigen and these vaccines are very efficient at producing tumour response
[63]
compared to peptide vaccines. The viruses used are adenoviruses, lentiviruses, poxviruses and retroviruses.

A phase I trial tested sequential vaccinations with fowlpox-CEA(6D)- TRICOM alone and sequentially with