Cancer immunoprevention

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Cancer immunoprevention is the prevention of cancer onset with immunological means such as vaccines, immunostimulators or antibodies. [1] [2] Cancer immunoprevention is conceptually different from cancer immunotherapy, which aims at stimulating immunity in patients only after tumor onset, however the same immunological means can be used both in immunoprevention and in immunotherapy.

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Immunoprevention of tumors caused by viruses

Immunoprevention of tumors caused by viruses or other infectious agents aims at preventing or curing infection before the onset of cancer. Effective vaccines are available for use in humans.
Some tumor types in humans and in animals are the consequence of viral infections. In humans the most frequent viral tumors are liver cancer (also called hepatocellular carcinoma), arising in a small proportion of patients with chronic infection by hepatitis B virus (HBV) or hepatitis C virus (HCV), and carcinoma of the uterine cervix (also called cervical cancer), caused by human papilloma virus (HPV). Altogether these two tumors make 10% of all human cancers, affecting almost one million new patients each year worldwide. [3] The HBV vaccine, now in worldwide use, was shown to reduce the incidence of liver carcinoma. [4] Cancer immunoprevention by the HBV vaccine can be thought of as a beneficial side effect of vaccine developed and used to prevent hepatitis B. This is not the case with HPV vaccines, which were primarily developed for cancer prevention. Clinical trials showed that HPV vaccines can prevent HPV infection and carcinogenesis almost completely; these results led to vaccine approval by regulatory agencies in USA and Europe. [5]

Immunoprevention of non-infectious tumors

Is it possible to devise immunopreventive strategies for tumors not caused by infectious agents? The challenge is to predict in each individual the risk of specific cancer types and to design immune strategies targeting these cancer types. This is not yet feasible in humans, thus immunoprevention of non-infectious tumors is at a preclinical stage of development.
Effective immunoprevention of various types of cancer was obtained in murine models of cancer risk, in particular in transgenic mice harboring activated oncogenes, thus demonstrating that activation of the immune system in healthy hosts can indeed prevent carcinogenesis. [1] Both non-specific immune stimuli, like cytokines and other immunostimulators, and vaccines containing a specific antigen were active in mouse models; combinations of both types of agents yielded the best results, up to an almost complete, long-term block of carcinogenesis in models of aggressive cancer development. [6]

Immune mechanisms

Two main protective mechanisms elicited by cancer immunoprevention in various mouse models were cytokines released by T cells, in particular gamma-interferon, and cytotoxic antibodies against the target antigen. This is at variance with cancer immunotherapy administered to cure existing tumors, which is mainly based on cytotoxic T lymphocytes (CTL). The lack of a relevant CTL response in long-term immunoprevention is thought to be an advantage, because chronic CTL activation is severely toxic for the host. In contrast circulating antibodies provide long-term protection without toxic side effects. A similar situation happens in viral immunity, acute infections are resolved by CTL, whereas long term immunity from reinfection is provided by antibodies.
Both gamma-interferon and antibodies prevent tumor growth in multiple ways. Gamma-interferon activates T, natural killer and B cells, inhibits angiogenesis and tumor invasiveness, stimulates major histocompatibility complex expression in tumor cells and inhibits cell proliferation. Antibodies binding to antigens on the surface of cells trigger lytic mechanisms mediated by the complement system (complement-mediated cytotoxicity) or by leukocytes carrying Fc receptors (antibody-dependent cell-mediated cytotoxicity, ADCC). Moreover, antibody binding interferes with the cellular functions of the target antigen, causing its internalization or hampering molecular interactions, eventually blocking downstream signaling. If the target antigen controls cell growth (e.g. if it is the product of an oncogene), then a block of signaling can disrupt the carcinogenic process. Surface antigens causally involved in carcinogenesis are called oncoantigens.[ citation needed ]

Clinical development and risks

The success of cancer immunoprevention in preclinical models suggests that it might have an impact also in humans. The main problems to be solved are the definition of appropriate human applications and of the risks for human health.
Application to the general population, as is being done for vaccines against HBV and HPV, is currently unfeasible, because it would require a precise individual prediction of the risk of cancer. Subgroups at high risk of developing a defined type of tumor, for example families with hereditary cancer or individuals with preneoplastic lesions, are the natural candidates for immunoprevention of non-infectious tumors. It has also been suggested that immunopreventive strategies can have therapeutic effects against metastases, hence early human trials could aim at cancer therapy rather than prevention. [2] [7]
The main risk of prolonged immune stimulation for cancer prevention is the development of autoimmune diseases. Most antitumor immune responses are autoimmune, because most tumor antigens are also expressed by normal cells, but it must be considered that autoimmune responses do not necessarily evolve into autoimmune diseases. The limited autoimmunity triggered by cancer immunoprevention did not cause overt autoimmune diseases in preclinical mouse studies, however this is an issue that will require careful monitoring in early clinical trials. [1]

Related Research Articles

Antigen Molecule triggering an immune response (antibody production) in the host

In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. The term antigen originally referred to a substance that is an antibody generator. Antigens can be proteins, peptides, polysaccharides, lipids, or nucleic acids.

Hepatitis Inflammation of the liver

Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain, and diarrhea. Hepatitis is acute if it resolves within six months, and chronic if it lasts longer than six months. Acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure. Chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer.

DNA vaccine Vaccine containing DNA

A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.

Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies.

Viral hepatitis Hepatitis that involves viral infection causing inflammation of the liver

Viral hepatitis is liver inflammation due to a viral infection. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form.

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

This is a list of AIDS-related topics, many of which were originally taken from the public domain U.S. Department of Health Glossary of HIV/AIDS-Related Terms, 4th Edition.

Oncovirus Viruses that can cause cancer

An oncovirus or oncogenic virus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, when the term "oncornaviruses" was used to denote their RNA virus origin. With the letters "RNA" removed, it now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor virus" or "cancer virus". The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the retinoblastoma protein.

Cancer immunotherapy Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy is the stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspeciality of oncology.

Liver cancer Medical condition

Liver cancer is cancer that starts in the liver. Liver cancer can be primary or secondary. Liver metastasis is more common than that which starts in the liver. Liver cancer is increasing globally.

Hepatitis B vaccine Vaccine against hepatitis B

Hepatitis B vaccine is a vaccine that prevents hepatitis B. The first dose is recommended within 24 hours of birth with either two or three more doses given after that. This includes those with poor immune function such as from HIV/AIDS and those born premature. It is also recommended that health-care workers be vaccinated. In healthy people routine immunization results in more than 95% of people being protected.

Cancer immunology

Cancer immunology is an interdisciplinary branch of biology that is concerned with understanding the role of the immune system in the progression and development of cancer; the most well known application is cancer immunotherapy, which utilises the immune system as a treatment for cancer. Cancer immunosurveillance and immunoediting are based on protection against development of tumors in animal systems and (ii) identification of targets for immune recognition of human cancer.

An oncoantigen is a surface or soluble tumor antigen that supports tumor growth. A major problem of cancer immunotherapy is the selection of tumor cell variants that escape immune recognition. The notion of oncoantigen was set forth in the context of cancer immunoprevention to define a class of persistent tumor antigens not prone to escape from immune recognition.

Hepatitis B Human viral infection

Hepatitis B is an infectious disease caused by the hepatitis B virus (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.

Nventa Biopharmaceuticals Corporation Canadian healthcare company

Nventa Biopharmaceuticals Corporation was a Canadian-incorporated biopharmaceutical company headquartered in San Diego, California developing therapeutics for the treatment of viral infections and cancer, focusing on diseases caused by human papillomavirus (HPV). Nventa is currently the only company applying heat shock protein (Hsp) technology to target the over 20 million Americans already infected with HPV. Previously headquartered in Victoria, British Columbia, Canada, the company’s common stock traded on the Toronto Stock Exchange under the symbol: NVN.

A hepatitis C vaccine, a vaccine capable of protecting against the hepatitis C virus (HCV), is not yet available. Although vaccines exist for hepatitis A and hepatitis B, development of an HCV vaccine has presented challenges. No vaccine is currently available, but several vaccines are currently under development.

Active immunotherapy is a type of immunotherapy that aims to stimulate the host's immune system or a specific immune response to a disease or pathogen and is most commonly used in cancer treatments. Active immunotherapy is also used for treatment of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, prion disease, and multiple sclerosis. Active immunotherapies induce an immune response through direct immune system stimulation, while immunotherapies that administer antibodies directly to the system are classified as passive immunotherapies. Active immunotherapies can elicit generic and specific immune responses depending on the goal of the treatment. The categories of active immunotherapy divide into:

Peptide-based synthetic vaccines, also called epitope vaccines, are subunit vaccines made from peptides. The peptides mimic the epitopes of the antigen that triggers direct or potent immune responses. Peptide vaccines can not only induce protection against infectious pathogens and non-infectious diseases but also be utilized as therapeutic cancer vaccines, where peptides from tumor-associated antigens are used to induce an effective anti-tumor T-cell response.

Neuvenge, Lapuleucel-T, is a therapeutic cancer vaccine (TCV) in development by Dendreon (DNDN). It uses the "immunotherapy platform approach" first successfully demonstrated on the U.S. Food and Drug Administration (FDA)-approved TCV Provenge. It was first tested on breast cancer patients with tumors expressing HER2/neu, and is now scheduled to be tested on bladder cancer patients.

Infectious causes of cancer

Estimates place the worldwide risk of cancers from infectious causes at 16.1%. Viral infections are risk factors for cervical cancer, 80% of liver cancers, and 15–20% of the other cancers. This proportion varies in different regions of the world from a high of 32.7% in Sub-Saharan Africa to 3.3% in Australia and New Zealand. Helicobacter pylori is associated with stomach cancer, and Mycobacterium, some other bacteria and parasites also have an effect.

References

  1. 1 2 3 P.-L. Lollini et al., Vaccines for tumour prevention, Nat. Rev. Cancer 6: 204-216, 2006. doi : 10.1038/nrc1815
  2. 1 2 P.-L. Lollini et al., Cancer immunoprevention, Future Oncol. 1: 57-66, 2005. doi : 10.1517/14796694.1.1.57
  3. ↑ B.W. Stewart & A.S. Coates, Cancer prevention: A global perspective. J. Clin. Oncol. 23: 392-403, 2005. doi : 10.1200/JCO.2005.05.132
  4. ↑ M.-H. Chang et al., Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. N. Engl. J. Med 336: 1855-1859, 1997.
  5. ↑ C.M. Wheeler, Advances in primary and secondary interventions for cervical cancer: human papillomavirus prophylactic vaccines and testing., Nature Clinical Practice Oncology 4, 224-235, 2007. doi : 10.1038/ncponc0770
  6. ↑ P. Nanni et al.. Combined allogeneic tumor cell vaccination and systemic interleukin 12 prevents mammary carcinogenesis in HER-2/neu transgenic mice. J. Exp. Med. 194: 1195-1206, 2001. doi : 10.1084/jem.194.9.1195
  7. ↑ P. Nanni et al., Antimetastatic activity of a preventive cancer vaccine. Cancer Res. 67: 11037-11044, 2007. doi : 10.1158/0008-5472.CAN-07-2499
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