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.

Contents

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]

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]

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<span class="mw-page-title-main">Hepatitis</span> 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.

<span class="mw-page-title-main">Human papillomavirus infection</span> Human disease

Human papillomavirus infection is caused by a DNA virus from the Papillomaviridae family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and results in either warts or precancerous lesions. These lesions, depending on the site affected, increase the risk of cancer of the cervix, vulva, vagina, penis, anus, mouth, tonsils, or throat. Nearly all cervical cancer is due to HPV, and two strains – HPV16 and HPV18 – account for 70% of all cases. HPV16 is responsible for almost 90% of HPV-positive oropharyngeal cancers. Between 60% and 90% of the other cancers listed above are also linked to HPV. HPV6 and HPV11 are common causes of genital warts and laryngeal papillomatosis.

<span class="mw-page-title-main">Anal cancer</span> Medical condition

Anal cancer is a cancer which arises from the anus, the distal opening of the gastrointestinal tract. Symptoms may include bleeding from the anus or a lump near the anus. Other symptoms may include pain, itchiness, or discharge from the anus. A change in bowel movements may also occur.

<span class="mw-page-title-main">Viral hepatitis</span> Liver inflammation from a viral infection

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, typically progressing from a long-lasting asymptomatic condition up to a decompensated hepatic disease and hepatocellular carcinoma (HCC).

A cancer vaccine, or oncovaccine, is a vaccine that either treats existing cancer or prevents development of cancer. 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.

<span class="mw-page-title-main">Liver disease</span> Medical condition

Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.

Post-exposure prophylaxis, also known as post-exposure prevention (PEP), is any preventive medical treatment started after exposure to a pathogen in order to prevent the infection from occurring.

<span class="mw-page-title-main">Oncovirus</span> 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.

<span class="mw-page-title-main">Liver cancer</span> Medical condition

Liver cancer, also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy, is cancer that starts in the liver. Liver cancer can be primary in which the cancer starts in the liver, or it can be liver metastasis, or secondary, in which the cancer spreads from elsewhere in the body to the liver. Liver metastasis is the more common of the two liver cancers. Instances of liver cancer are increasing globally.

<span class="mw-page-title-main">Hepatitis B vaccine</span> 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.

<span class="mw-page-title-main">Toll-like receptor 9</span> Protein found in humans

Toll-like receptor 9 is a protein that in humans is encoded by the TLR9 gene. TLR9 has also been designated as CD289. It is a member of the toll-like receptor (TLR) family. TLR9 is an important receptor expressed in immune system cells including dendritic cells, macrophages, natural killer cells, and other antigen presenting cells. TLR9 is expressed on endosomes internalized from the plasma membrane, binds DNA, and triggers signaling cascades that lead to a pro-inflammatory cytokine response. Cancer, infection, and tissue damage can all modulate TLR9 expression and activation. TLR9 is also an important factor in autoimmune diseases, and there is active research into synthetic TLR9 agonists and antagonists that help regulate autoimmune inflammation.

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.

<span class="mw-page-title-main">Hepatitis B</span> 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.

Merkel cell polyomavirus was first described in January 2008 in Pittsburgh, Pennsylvania. It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called digital transcriptome subtraction. MCV is one of seven currently known human oncoviruses. It is suspected to cause the majority of cases of Merkel cell carcinoma, a rare but aggressive form of skin cancer. Approximately 80% of Merkel cell carcinoma (MCC) tumors have been found to be infected with MCV. MCV appears to be a common—if not universal—infection of older children and adults. It is found in respiratory secretions, suggesting that it might be transmitted via a respiratory route. However, it has also been found elsewhere, such as in shedded healthy skin and gastrointestinal tract tissues, thus its precise mode of transmission remains unknown. In addition, recent studies suggest that this virus may latently infect the human sera and peripheral blood mononuclear cells.

<i>Hepatitis B virus</i> Species of the genus Orthohepadnavirus

Hepatitis B virus (HBV) is a partially double-stranded DNA virus, a species of the genus Orthohepadnavirus and a member of the Hepadnaviridae family of viruses. This virus causes the disease hepatitis B.

<span class="mw-page-title-main">Infectious causes of cancer</span> Pathogens as a cause 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.

Cancer is caused by genetic changes leading to uncontrolled cell growth and tumor formation. The basic cause of sporadic (non-familial) cancers is DNA damage and genomic instability. A minority of cancers are due to inherited genetic mutations. Most cancers are related to environmental, lifestyle, or behavioral exposures. Cancer is generally not contagious in humans, though it can be caused by oncoviruses and cancer bacteria. The term "environmental", as used by cancer researchers, refers to everything outside the body that interacts with humans. The environment is not limited to the biophysical environment, but also includes lifestyle and behavioral factors.

Robert Palmer Beasley was an American physician, public health educator and epidemiologist whose work on hepatitis B involved extensive investigations in Taiwan. That work established that hepatitis B virus (HBV) is a primary cause of liver cancer and that hepatitis B virus is transmitted from mother to infant during childbirth. Beasley and his colleagues also proved that HBV mother-to-infant transmission is preventable by at-birth vaccination. Due to this work, the World Health Assembly designated HBV as the seventh global vaccine in 1992. He later became the author of HBV immunization policies for the World Health Organization.

<span class="mw-page-title-main">Neonatal infection</span> Human disease

Neonatal infections are infections of the neonate (newborn) acquired during prenatal development or within the first four weeks of life. Neonatal infections may be contracted by mother to child transmission, in the birth canal during childbirth, or after birth. Neonatal infections may present soon after delivery, or take several weeks to show symptoms. Some neonatal infections such as HIV, hepatitis B, and malaria do not become apparent until much later. Signs and symptoms of infection may include respiratory distress, temperature instability, irritability, poor feeding, failure to thrive, persistent crying and skin rashes.

<i>Woolly monkey hepatitis B virus</i> Species of virus

The woolly monkey hepatitis B virus (WMHBV) is a viral species of the Orthohepadnavirus genus of the Hepadnaviridae family. Its natural host is the woolly monkey (Lagothrix), an inhabitant of South America categorized as a New World primate. WMHBV, like other hepatitis viruses, infects the hepatocytes, or liver cells, of its host organism. It can cause hepatitis, liver necrosis, cirrhosis, and hepatocellular carcinoma. Because nearly all species of Lagothrix are threatened or endangered, researching and developing a vaccine and/or treatment for WMHBV is important for the protection of the whole woolly monkey genus.

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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