A cancer vaccine is a vaccine that either treats existing cancer or prevents development of cancer.[1] Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.

Some researchers claim that cancerous cells routinely arise and are destroyed by the immune system (immunosurveillance);[2] and that tumors form when the immune system fails to destroy them.[3]

Some types of cancer, such as cervical cancer and liver cancer, are caused by viruses (oncoviruses). Traditional vaccines against those viruses, such as the HPV vaccine[4] and the hepatitis B vaccine, prevent those types of cancer. Other cancers are to some extent caused by bacterial infections (e.g. stomach cancer and Helicobacter pylori[5]). Traditional vaccines against cancer-causing bacteria (oncobacteria) are not further discussed in this article.


One approach to cancer vaccination is to separate proteins from cancer cells and immunize patients against those proteins as antigens, in the hope of stimulating the immune system to kill the cancer cells. Research on cancer vaccines is underway for treatment of breast, lung, colon, skin, kidney, prostate and other cancers.[6]

Another approach is to generate an immune response in situ in the patient using oncolytic viruses. This approach was used in the drug talimogene laherparepvec, a variant of herpes simplex virus engineered to selectively replicate in tumor tissue and to express the immune stimulatory protein GM-CSF. This enhances the anti-tumor immune response to tumor antigens released following viral lysis and provides a patient-specific vaccine.[7]

Mechanism of action

Tumor antigen vaccines work the same way that viral vaccines work, by training the immune system to attack cells that contain the antigens in the vaccine. The difference is that the antigens for viral vaccines are derived from viruses or cells infected with virus, while the antigens for tumor antigen vaccines are derived from cancer cells. Since tumor antigens are antigens found in cancer cells but not normal cells, vaccinations containing tumor antigens should train the immune system to target cancer cells not healthy cells. Cancer-specific tumor antigens include peptides from proteins that are not typically found in normal cells but are activated in cancer cells or peptides containing cancer-specific mutations. Antigen-presenting cells (APCs) such as dendritic cells take up antigens from the vaccine, process them into epitopes, and present the epitopes to T-cells via Major Histocompatibility Complex proteins. If T-cells recognize the epitope as foreign, the adaptive immune system is activated and target cells that express the antigens.[8]

Prevention vs. treatment

Viral vaccines usually work by preventing the spread of the virus. Similarly, cancer vaccines can be designed to target common antigens before cancer evolves if an individual has appropriate risk factors. Additional preventive applications include preventing the cancer from evolving further or undergoing metastasis and preventing relapse after remission. Therapeutic vaccines focus on killing existing tumors. While cancer vaccines have generally been demonstrated to be safe, their efficacy still needs improvement. One way to potentially improve vaccine therapy is by combining the vaccine with other types of immunotherapy aimed at stimulating the immune system. Since tumors often evolve mechanisms to suppress the immune system, immune checkpoint blockade has recently received a lot of attention as a potential treatment to be combined with vaccines. For therapeutic vaccines, combined therapies can be more aggressive, but greater care to ensure the safety of relatively healthy patients is needed for combinations involving preventive vaccines.[9]


Cancer vaccines can be cell-based, protein- or peptide-based, or gene-based (DNA/RNA).[9]

Cell-based vaccines include tumor cells or tumor cell lysates. Tumor cells from the patient are predicted to contain the greatest spectrum of relevant antigens, but this approach is expensive and often requires too many tumor cells from the patient to be effective.[10] Using a combination of established cancer cell lines that resemble the patient’s tumor can overcome these barriers, but this approach has yet to be effective. Canvaxin, which incorporates three melanoma cell lines, failed phase III clinical trials.[10] Another cell-based vaccine strategy involves autologous dendritic cells (dendritic cells derived from the patient) to which tumor antigens are added. In this strategy, the antigen-presenting dendritic cells directly stimulate T-cells rather than relying on processing of the antigens by native APCs after the vaccine is delivered. The best known dendritic cell vaccine is Sipuleucel-T (Provenge), which only improved survival by four months. The efficacy of dendritic cell vaccines may be limited due to difficulty in getting the cells to migrate to lymph nodes and interact with T-cells.[9]

Peptide-based vaccines usually consist of cancer specific-epitopes and often require an adjuvant (for example, GM-CSF) to stimulate the immune system and enhance antigenicity.[8] Examples of these epitopes include Her2 peptides, such as GP2 and NeuVax. However, this approach requires MHC profiling of the patient because of MHC restriction.[11] The need for MHC profile selection can be overcome by using longer peptides (“synthetic long peptides”) or purified protein, which are then processed into epitopes by APCs.[11]

Gene-based vaccines are composed of the nucleic acid (DNA/RNA) encoding for the gene. The gene is then expressed in APCs and the resulting protein product is processed into epitopes. Delivery of the gene is particularly challenging for this type of vaccine.[9]

Clinical trials

The clinicaltrials.gov website lists over 1900 trials associated with the term “cancer vaccine”. Of these, 186 are Phase 3 trials.

The following table, summarizing information from another recent review shows an example of the antigen used in the vaccine tested in Phase 1/2 clinical trials for each of 10 different cancers:[10]

Cancer type Antigen
Bladder cancer NY-ESO-1
Breast cancer HER2
Cervical cancer HPV16 E7 (Papillomaviridae#E7)
Colorectal cancer CEA (Carcinoembryonic antigen)
Leukemia WT1
Melanoma MART-1, gp100, and tyrosinase
Non small lung cell cancer (NSCLC) URLC10, VEGFR1, and VEGFR2
Ovarian cancer survivin
Pancreatic cancer MUC1
Prostate cancer MUC2

Approved oncovaccines

Oncophage was approved in Russia in 2008 for kidney cancer. It is marketed by Antigenics Inc.[citation needed]

Sipuleucel-T, Provenge, was approved by the FDA in April 2010 for metastatic hormone-refractory prostate cancer. It is marketed by Dendreon Corp.

Bacillus Calmette-Guérin (BCG) was approved by the FDA in 1990 as a vaccine for early-stage bladder cancer.[15] BCG can be administered intravesically (directly into the bladder) or as an adjuvant in other cancer vaccines.

Abandoned research

CancerVax (Canvaxin), Genitope Corp (MyVax personalized immunotherapy), and FavId FavId (Favrille Inc) are examples of cancer vaccine projects that have been terminated, due to poor phase III and IV results.[citation needed]

Desirable characteristics

Cancer vaccines seek to target a tumor-specific antigen as distinct from self-proteins. Selection of the appropriate adjuvant to activate antigen-presenting cells to stimulate immune responses, is required. Bacillus Calmette-Guérin, an aluminum-based salt, and a squalene-oil-water emulsion are approved for clinical use. An effective vaccine should also stimulate long term immune memory to prevent tumor recurrence. Some scientists claim both the innate and adaptive immune systems must be activated to achieve total tumor elimination.[16]

Antigen candidates

Tumor antigens have been divided into two categories: shared tumor antigens; and unique tumor antigens. Shared antigens are expressed by many tumors. Unique tumor antigens result from mutations induced through physical or chemical carcinogens; they are therefore expressed only by individual tumors.

In one approach, vaccines contain whole tumor cells, though these vaccines have been less effective in eliciting immune responses in spontaneous cancer models. Defined tumor antigens decrease the risk of autoimmunity, but because the immune response is directed to a single epitope, tumors can evade destruction through antigen loss variance. A process called "epitope spreading" or "provoked immunity" may mitigate this weakness, as sometimes an immune response to a single antigen can lead to immunity against other antigens on the same tumor.[16]

For example, since Hsp70 plays an important role in the presentation of antigens of destroyed cells including cancer cells,[17] this protein may be used as an effective adjuvant in the development of antitumor vaccines.[18]

Hypothesized problems

A vaccine against a particular virus is relatively easy to create. The virus is foreign to the body, and therefore expresses antigens that the immune system can recognize. Furthermore, viruses usually only provide a few viable variants. By contrast, developing vaccines for viruses that mutate constantly such as influenza or HIV has been problematic. A tumor can have many cell types of cells, each with different cell-surface antigens. Those cells are derived from each patient and display few if any antigens that are foreign to that individual. This makes it difficult for the immune system to distinguish cancer cells from normal cells. Some scientists believe that renal cancer and melanoma are the two cancers with most evidence of spontaneous and effective immune responses, possibly because they often display antigens that are evaluated as foreign. Many attempts at developing cancer vaccines are directed against these tumors. However, Provenge's success in prostate cancer, a disease that never spontaneously regresses, suggests that cancers other than melanoma and renal cancer may be equally amenable to immune attack.[citation needed]

However, most vaccine clinical trials have failed or had modest results according to the standard RECIST criteria.[19] The precise reasons are unknown, but possible explanations include:


In January 2009, a review article made recommendations for successful oncovaccine development as follows:[20]

See also


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  2. ^ Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD (April 2001). "IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity". Nature. 410 (6832): 1107–1111. Bibcode:2001Natur.410.1107S. doi:10.1038/35074122. PMID 11323675. S2CID 205016599.
  3. ^ Dunn GP, Old LJ, Schreiber RD (2004). "The three Es of cancer immunoediting". Annual Review of Immunology. 22 (i): 329–360. doi:10.1146/annurev.immunol.22.012703.104803. PMID 15032581.
  4. ^ Babu RA, Kumar KK, Reddy GS, Anuradha C (2010). "Cancer Vaccine : A Review" (PDF). Journal of Orofacial Sciences. 2 (3): 77–82. Archived from the original (PDF) on 2019-06-30.
  5. ^ "Oral vaccine could fight source of stomach cancers". Vaccine News Reports. Archived from the original on 2015-04-24. Retrieved 2010-06-22.
  6. ^ Giarelli E (October 2007). "Cancer vaccines: a new frontier in prevention and treatment". Oncology. 21 (11 Suppl Nurse Ed): 11–7, discussion 18. PMID 18154203.
  7. ^ a b Amgen press release. Amgen announces top-line results of phase 3 talimogene laherparepvec trial in melanoma. Mar 19, 2013. Available here
  8. ^ a b Sayour EJ, Mitchell DA (2017-02-06). "Manipulation of Innate and Adaptive Immunity through Cancer Vaccines". Journal of Immunology Research. 2017: 3145742. doi:10.1155/2017/3145742. PMC 5317152. PMID 28265580.
  9. ^ a b c d Lollini PL, Cavallo F, Nanni P, Quaglino E (June 2015). "The Promise of Preventive Cancer Vaccines". Vaccines. 3 (2): 467–489. doi:10.3390/vaccines3020467. PMC 4494347. PMID 26343198.
  10. ^ a b c Tagliamonte M, Petrizzo A, Tornesello ML, Buonaguro FM, Buonaguro L (2014-10-31). "Antigen-specific vaccines for cancer treatment". Human Vaccines & Immunotherapeutics. 10 (11): 3332–3346. doi:10.4161/21645515.2014.973317. PMC 4514024. PMID 25483639.
  11. ^ a b c Pol J, Bloy N, Buqué A, Eggermont A, Cremer I, Sautès-Fridman C, et al. (April 2015). "Trial Watch: Peptide-based anticancer vaccines". Oncoimmunology. 4 (4): e974411. doi:10.4161/2162402X.2014.974411. PMC 4485775. PMID 26137405.
  12. ^ Idiotype vaccine therapy (BiovaxID) in follicular lymphoma in first complete remission: Phase III clinical trial results. Archived 2011-09-27 at the Wayback Machine S. J. Schuster, et al. 2009 ASCO Annual Meeting, J Clin Oncol 27:18s, 2009 (suppl; abstr 2)
  13. ^ "Approval Letter - Provenge". Food and Drug Administration. 2010-04-29.
  14. ^ "What Comes After Dendreon's Provenge?". 18 Oct 2010.
  15. ^ "Immunotherapy for Bladder Cancer". Cancer Research Institute. Retrieved 2019-10-13.
  16. ^ a b Pejawar-Gaddy S, Finn OJ (August 2008). "Cancer vaccines: accomplishments and challenges". Critical Reviews in Oncology/Hematology. 67 (2): 93–102. doi:10.1016/j.critrevonc.2008.02.010. PMID 18400507.
  17. ^ Nishikawa M, Takemoto S, Takakura Y (April 2008). "Heat shock protein derivatives for delivery of antigens to antigen presenting cells". International Journal of Pharmaceutics. Special Issue in Honor of Prof. Tsuneji Nagai. 354 (1–2): 23–27. doi:10.1016/j.ijpharm.2007.09.030. PMID 17980980.
  18. ^ Savvateeva LV, Schwartz AM, Gorshkova LB, Gorokhovets NV, Makarov VA, Reddy VP, et al. (2015-01-01). "Prophylactic Admission of an In Vitro Reconstructed Complexes of Human Recombinant Heat Shock Proteins and Melanoma Antigenic Peptides Activates Anti-Melanoma Responses in Mice". Current Molecular Medicine. 15 (5): 462–468. doi:10.2174/1566524015666150630125024. PMID 26122656.
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