Cancer vaccine

Source: Wikipedia, the free encyclopedia.

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 (

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.

Method

One approach to cancer vaccination is to separate proteins from cancer cells and immunize patients against those proteins as

colon, skin, kidney, prostate and other cancers.[6]

Another approach is to generate an immune response

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

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

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]

Types

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

lymph nodes and interact with T-cells.[9]

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

mRNA vaccines for use in this application.[12][13]

Clinical trials

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

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]

hormone-refractory prostate cancer. It is marketed by Dendreon
Corp.

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

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.[21]

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

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.[24]
The precise reasons are unknown, but possible explanations include:

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

References

  1. PMID 34661150
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  2. .
  3. .
  4. .
  5. ^ "Oral vaccine could fight source of stomach cancers". Vaccine News Reports. Archived from the original on 24 April 2015. Retrieved 22 June 2010.
  6. 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 Archived 21 January 2014 at the Wayback Machine
  8. ^
    PMID 28265580
    .
  9. ^ .
  10. ^ .
  11. ^ .
  12. .
  13. .
  14. ^ 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)
  15. ^ "Approval Letter - Provenge". Food and Drug Administration. 29 April 2010. Archived from the original on 23 July 2017. Retrieved 16 December 2019.
  16. ^ "What Comes After Dendreon's Provenge?". 18 October 2010. Archived from the original on 14 August 2016. Retrieved 18 October 2010.
  17. ^ 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.
  18. ^ "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.
  19. ^ "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.
  20. ^ "Immunotherapy for Bladder Cancer". Cancer Research Institute. Archived from the original on 13 October 2019. Retrieved 13 October 2019.
  21. ^
    PMID 18400507
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  22. .
  23. .
  24. .
  25. .

External links