Cancer vaccine
A cancer vaccine, or oncovaccine, 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 (
Some
Method
One approach to cancer vaccination is to separate proteins from cancer cells and immunize patients against those proteins as
Another approach is to generate an immune response
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
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
Types
Cancer vaccines can be cell-based, protein- or peptide-based, or gene-based (DNA/RNA).[9]
Gene-based vaccines are composed of the
Clinical trials
This section needs to be updated.(January 2024) |
The clinicaltrials.gov website lists over 1900 trials associated with the term “cancer vaccine”. Of these, 186 are Phase 3 trials.[when?]
- In a BiovaxID (on average) prolonged remission by 44.2 months, versus 30.6 months for the control.[14]
- On April 14, 2009,
- Interim results from a phase III trial of talimogene laherparepvec in melanoma showed a significant tumour response compared to administration of GM-CSF alone.[7]
- A recent Trial Watch review (2015) of peptide-based vaccines summarized the results of more than 60 trials that were published in the 13 months preceding the article.FLT1 and KDR. Notably, the IDO1 vaccine is being tested in patients with melanoma in combination with the immune checkpoint inhibitor ipilimumab and the BRAF (gene) inhibitor vemurafenib.
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 | gp100, and tyrosinase
|
Non small lung cell cancer ( NSCLC ) |
URLC10, 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]
CimaVax-EGF was approved in Cuba in 2011.[17] Similar to Oncophage, it is not yet approved for use in the United States, although it is already undergoing phase II trials to that end.[18][19]
Bacillus Calmette-Guérin (BCG) was approved by the FDA in 1990 as a vaccine for early-stage bladder cancer.[20] 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 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.[21]
For example, since Hsp70 plays an important role in the presentation of antigens of destroyed cells including cancer cells,[22] this protein may be used as an effective adjuvant in the development of antitumor vaccines.[23]
Hypothesized problems
A vaccine against a particular virus is relatively easy to create. The virus is foreign to the body, and therefore expresses
However, most vaccine clinical trials have failed or had modest results according to the standard
- Disease stage too advanced: bulky tumor deposits actively suppress the immune system using mechanisms such as secretion of cytokinesthat inhibit immune activity. The most suitable stage for a cancer vaccine is likely to be early, when the tumor volume is low, which complicates the trial process, which take upwards of five years and require many patients to reach measurable end points. One alternative is to target patients with residual disease after surgery, radiotherapy or chemotherapy that does not harm the immune system.
- Escape loss variants (that target a single tumor antigen) are likely to be less effective. Tumors are heterogeneous and antigen expression differs markedly between tumors (even in the same patient). The most effective vaccine is likely to raise an immune response against a broad range of tumor antigens to minimise the chance of the tumor mutating and becoming resistant to the therapy.
- Prior treatments may have modified tumors in ways that nullify the vaccine. (Numerous clinical trials treated patients following chemotherapy that may destroy the immune system. Patients who are immune suppressed are not good candidates for vaccines.)
- Some tumors progress rapidly and/or unpredictably, and they can outpace the immune system. Developing a mature immune response to a vaccine may require months, but some cancers (e.g. advanced pancreatic) can kill patients in less time.
- Many cancer vaccine clinical trials target patients' immune responses. Correlations typically show that the patients with the strongest immune responses lived the longest, offering evidence that the vaccine is working. An alternative explanation is that patients with the best immune responses were healthier patients with a better prognosis, and would have survived longest even without the vaccine.
Recommendations
In January 2009, a review article made recommendations for successful oncovaccine development as follows:[25]
- Target settings with a low disease burden.
- Conduct randomized Phase II trials so that the Phase III program is sufficiently powered.
- Do not randomize antigen plus adjuvant versus adjuvant alone. The goal is to establish clinical benefit of the immunotherapy (i.e., adjuvanted vaccine) over the standard of care. The adjuvant may have a low-level clinical effect that skews the trial, increasing the chances of a false negative.
- Base development decisions on clinical data rather than immune responses. Time-to-event end points are more valuable and clinically relevant.
- Design regulatory into the program from inception; invest in manufacturing and product assays early.
See also
- Immunotherapy
- Cancer immunotherapy
- Chemoprophylaxis
- HPV vaccines
- Therapeutic vaccines
References
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- S2CID 205016599.
- PMID 15032581.
- S2CID 68256825.
- ^ "Oral vaccine could fight source of stomach cancers". Vaccine News Reports. Archived from the original on 24 April 2015. Retrieved 22 June 2010.
- PMID 18154203.
- ^ a b Amgen press release. Amgen announces top-line results of phase 3 talimogene laherparepvec trial in melanoma. Mar 19, 2013. Available here Archived 21 January 2014 at the Wayback Machine
- ^ PMID 28265580.
- ^ PMID 26343198.
- ^ PMID 25483639.
- ^ PMID 26137405.
- S2CID 259184146.
- PMID 36992220.
- ^ 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)
- ^ "Approval Letter - Provenge". Food and Drug Administration. 29 April 2010. Archived from the original on 23 July 2017. Retrieved 16 December 2019.
- ^ "What Comes After Dendreon's Provenge?". 18 October 2010. Archived from the original on 14 August 2016. Retrieved 18 October 2010.
- ^ Dillow, Clay (8 September 2011). "Cuba Announces Release of the World's First Lung Cancer Vaccine". Popular Science. Archived from the original on 25 August 2017. Retrieved 12 May 2023.
- ^ "Roswell Park Lung Cancer Expert Shares Initial Findings From First North American Study of CIMAvax". Roswell Park Comprehensive Cancer Center. 26 September 2018. Archived from the original on 12 May 2023. Retrieved 12 May 2023.
- ^ "With Safety Analysis Now Complete, Roswell Park Moves Forward With Expanded Study of CIMAvax". Roswell Park Comprehensive Cancer Center. 30 March 2019. Archived from the original on 12 May 2023. Retrieved 12 May 2023.
- ^ "Immunotherapy for Bladder Cancer". Cancer Research Institute. Archived from the original on 13 October 2019. Retrieved 13 October 2019.
- ^ PMID 18400507.
- PMID 17980980.
- PMID 26122656.
- PMID 15340416.
- S2CID 26656379.
External links
- Cancer Immunotherapy Consortium (coordinated early-phase clinical trials of therapeutic cancer vaccines)
- Society for Immunotherapy of Cancer
- Association for the Immunotherapy of Cancer
- Tumor antigen vaccine entry in the public domain NCI Dictionary of Cancer Terms
- List of cancer vaccine clinical trials at clinicaltrials.gov.