Table 2.
Overview of literature findings and proposed next steps for vaccines with repurposing potential in oncology.
| Vaccine | Type | Trials | Summary of the main literature findings | Proposed next steps |
|---|---|---|---|---|
| BCG vaccine | Live attenuated bacterium | 15 registered but many trials preceded trial registries | BCG has been extensively used as an adjuvant to cancer vaccines (autologous cancer cells or dendritic cells-based) without any clinical success so far. Intratumoral BCG is listed in melanoma guidelines and is used in spontaneous cancers in large animals. This supports combining BCG with other drugs in specific cancer types. However, the rather nonspecific immune stimulation induced by BCG may make BCG less attractive than other intratumoral immunomodulators. | Early-phase clinical trials combining intratumoral BCG injections with approved therapies. |
| Cholera vaccine | Inactivated/killed bacterium | None | Three positive pharmaco-epidemiologic studies in colorectal, prostate, and breast cancers. ‘Desirable’ immune and inflammatory changes induced by the vaccine observed in the colon in animal models. | Preclinical work in colorectal cancer models to further characterize efficacy and mode of action. If positive, preclinical work could extend to prostate and breast cancer models as well. |
| Diphtheria vaccine | Toxoid (inactivated bacterial toxin) | NCT03299309, NCT03927222, NCT03688178, NCT02193347, NCT03615404, NCT02366728, NCT02465268, NCT02338700, NCT02338752, NCT02338778, NCT02338804, NCT02333474 | The Td vaccine has been used to augment anti-tumor immune responses expected from experimental immunotherapies, with various proposed mechanisms. The first 7 trials listed use Td as a preconditioning strategy to augment the effect of experimental immunotherapies (either peptide vaccines or cell-based therapies) in patients with brain cancer. The other 5 trials (no results published) combine the diphtheria vaccine with other infectious disease vaccines in patients with prostate, pancreas, liver, breast or lung cancer. | Currently no next steps identified because awaiting trial results in brain, prostate, pancreas, liver, breast and lung cancer. |
| Hepatitis B vaccine | Inactivated virus/recombinant DNA | None | Limited evidence summarized in a review mainly building on the use of HBV antigens in cancer experiments. | Confirmation of a potentiating role of HBV vaccine with approved immunotherapies in preclinical models. |
| Human Papillomavirus vaccine | Viral subunit/conjugate | NCT03051516, NCT04096911 | Systemic responses observed in patients with SCC of the skin injected intratumorally and/or intramuscularly with HPV vaccines. The trials listed explore if HPV vaccine can prevent the recurrence of pre-cancerous anal or vulvar lesions, and, in combination with anti-PD1, treat incurable HPV+ cervical cancer. | In cutaneous SCC, an efficacy phase 2 trial might be an appropriate next step. With regards to HPV+ cervical cancer, results of the ongoing trial are to be awaited. |
| Influenza vaccine | Inactivated/killed virus, viral subunit/conjugate |
NCT02998736, NCT04591379 |
The ability of the vaccine to restore NK cell dysfunction induced by cancer surgery, shown in animal models of lung metastases, is being tested in patients with abdominal malignancies in the trial listed. A pilot trial of intratumoral injection before colorectal cancer surgery is also ongoing. Additional in vivo evidence for a role of intratumoral injection to improve anti-PD-1 efficacy in a murine melanoma model exists. | For peri-operative use in colorectal cancer or lung metastases, results of ongoing trials are awaited. Efficacy of intratumoral influenza vaccine in combination with immune checkpoint inhibitors could be investigated in an early phase trial involving melanoma and/or triple negative breast cancer patients. |
| Measles vaccine | Live attenuated virus | NCT00828022, (19) | Vaccine has been shown to be cytotoxic in multiple cancer cell lines with in vivo confirmation, most often (but not always) after intratumoral injection, in models of myeloma, lymphoma, leukemia, laryngeal, lung, melanoma, ovarian and prostate carcinoma. A trial of measles vaccine as consolidation therapy in lung cancer has not yet reported results, whereas a phase I trial of intratumoral injection in cutaneous T-cell lymphoma patients has shown its ability to induce tumor regression. |
Research strategy should be streamlined as research is currently going in multiple directions. Additional preclinical work and/or a phase I trial in an injectable tumor for which in vivo data exist, could be relevant, in addition to a phase 2 trial in T-cell lymphoma. Depending on the outcome of the phase 1/2 lung cancer trial, this strategy could also be further explored. |
| Mumps vaccine | Live attenuated virus | None | Supporting data in animal models of AML, ovarian and prostate cancer. | Additional preclinical work in ovarian cancer, perhaps in combination with the measles vaccine. |
| Pertussis vaccine | Bacterial subunit/conjugate Inactivated/killed bacterium |
None | A case report of a dramatic response in a melanoma patient after diphtheria-tetanus-pertussis vaccination. The pertussis vaccine has been used as an adjuvant to improve anti-tumor immune responses in animal models of lymphoma. | Preclinical work on the diphtheria-tetanus-pertussis vaccine in melanoma models and on the whole-cell pertussis vaccine in lymphoma. |
| Pneumococcus vaccine | Bacterial subunit/conjugate | (20), NCT01351896, NCT03376477, NCT03942328 | All ongoing and reported trials use the pneumococcus vaccine in combination with lenalidomide or experimental immunotherapies (cancer vaccines or autologous dendritic cells) to help eliciting anti-tumor responses in patients with chronic lymphocytic leukemia, lymphocytic lymphoma, multiple myeloma and liver cancer. | Currently none as trials are ongoing in chronic lymphocytic leukemia, lymphocytic lymphoma, multiple myeloma and liver cancer. Results to be awaited. |
| Rotavirus vaccine | Live attenuated virus | None | In a series of animal experiments, intratumoral injections of the rotavirus vaccine could overcome resistance to checkpoint inhibitors in 4 different models (neuroblastoma, lymphoma, breast and colon carcinoma) and strongly synergize with checkpoint inhibitors in a neuroblastoma and a lymphoma model. | A proof-of-concept trial in neuroblastoma and lymphoma is necessary. |
| Smallpox vaccine | Live attenuated virus | NCT04410874 | A positive observational study in melanoma patients. Attempts to vaccinate melanoma patients with a melanoma-vaccinia lysate have failed in randomized clinical trials. Canadian phase 1/2 trial is currently recruiting patients with basal cell carcinoma and squamous cell carcinoma for intratumoral treatment with a smallpox vaccine. | Currently none as trial in non-melanoma skin cancer is ongoing. |
| Tetanus vaccine | Toxoid (inactivated bacterial toxin) | (21, 22), NCT02366728, NCT02737475 | The Td vaccine has been used to augment anti-tumor immune responses expected from experimental immunotherapies, with various proposed mechanisms. One trial in colorectal cancer did not show any role for Td when added to an experimental cancer vaccine. One trial in glioblastoma suggests that priming DC with Td is beneficial. This led to an ongoing glioblastoma trial. The last trial uses Td with an experimental drug in advanced cancers (but no rationale is available). | Cf. Diphtheria vaccine |
| Typhoid vaccine | Live attenuated bacterium, bacterial subunit/conjugate | NCT03421236 (23), | Based on preclinical data in a mice model of bladder cancer showing an effect superior to the BCG vaccine, a phase I trial of intravesical instillations has been initiated in bladder cancer patients. DC therapy generated using a mix of BCG vaccine, typhoid vaccine and a vaccine against Haemophilus influenzae, plus prostaglandin E2 showed improved survival in stage IV melanoma patients. |
Currently none as bladder cancer trial is ongoing. |
| Varicella vaccine | Live attenuated virus | NCT01953900 | The VZV vaccine is used to expand experimental T-cells targeting GD-2 in a trial protocol in osteosarcoma and neuroblastoma. | Currently none as trial in neuroblastoma and osteosarcoma with the vaccine and anti-GD2 T-cell is ongoing. |
| Yellow Fever vaccine | Live attenuated virus | None | Mixed results from observational study in melanoma patients. Preclinical data supporting a role for intratumoral injection of the yellow fever vaccine in animal models of colon cancer and melanoma. | More preclinical work with animal models and a phase I trial in melanoma based on observational study and preclinical data. |
BCG, Bacillus Calmette–Guérin; Td, tetanus diphtheria; HBV, hepatitis B virus; HPV, human papillomavirus; SCC, squamous cell carcinoma; NK, natural killer; PD-1, programmed cell death protein 1; AML, acute myeloid leukemia; DC, dendritic cell; VZV, varicella-zoster virus; GD-2, disialoganglioside.