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Cancer Vaccines: A New Frontier in Prevention and Treatment

Cancer Vaccines: A New Frontier in Prevention and Treatment

ABSTRACT: Vaccines have been exceptionally effective against diseases such as smallpox, measles, chickenpox, and polio. They are among the safest and most cost-effective agents for disease prevention. In recent years, vaccination has been considered for other diseases, including AIDS and cancer. Cancer vaccines can be categorized as preventive or therapeutic. Preventive vaccines, which are commercially available for cervical cancer and liver cancer, block infection with the causative agents of human papillomavirus and hepatitis B virus, respectively. The benefit of cancer treatment vaccines lies in their ability to "boost" the immune system response to cancer cells, which is generally low. Using vaccines in the treatment of cancer is relatively new, however, and chiefly experimental. Therapeutic vaccines for breast, lung, colon, skin, renal, prostate, and other cancers are now being investigated in clinical trials. Oncology nurses may play a significant role in reducing barriers to uptake of preventive vaccines among the general public and in increasing patients' acceptance of therapeutic cancer vaccines.

Vaccines have been a part of medical practice for more than 200 years, since Edward Jenner developed an inoculation for smallpox in 1796.[1] Vaccination has been used routinely for decades in the US, with a typical American receiving his or her first vaccination at 1 week of age to protect against a variety of childhood illnesses. This once-novel treatment modality is now a common way of building up the immune system to fight infection. Vaccines have been exceptionally effective against smallpox, measles, chickenpox, and polio. They are among the safest and most cost-effective preventative agents.

The antibody (immune) response that cancer vaccines stimulate is the principal means by which they may limit or prevent carcinogenesis.[2] Though cancer is not considered an "infection," we know that some cancers are caused by infectious agents. For example, human papillomavirus (HPV) causes cervical and anogenital carcinomas,[3] and hepatitis B virus (HBV) is associated with hepatocellular carcinoma. Many clinical trials are under way to test vaccines as potential preventive and therapeutic agents for a variety of cancers. In particular, scientists from the National Cancer Institute are studying use of cytokines--endogenous small secreted proteins which mediate and regulate immune function, inflammation, and hematopoiesis--to increase the response of the immune system to experimental vaccines. Vaccinations for various types of common cancers are likely to be cost-effective if paired with effective cancer screening practices.[4]

The benefit of cancer treatment vaccines lies in their ability to "boost" the immune system response to cancer cells, which is generally low because tumors are not sufficiently different from normal cells to be recognized as foreign; cancer cells also may shed antigens or exert other immune-modulating effects that make them less vulnerable to attack by the body's immune system.

This article describes the state of the science of cancer vaccines, which are being developed both for primary prevention in healthy individuals (by stimulating the immune system to attack cancer-causing viruses, thereby preventing the viral infection) and as therapeutic agents for people already diagnosed with cancer, with therapeutic vaccines stimulating the body's immune system to target cancer calls without destroying healthy cells. Recommendations are made regarding roles of oncology nurses in this promising new avenue of cancer care.

Immune System Basics

The human immune system comprises several types of cells formed in the bone marrow that circulate through the lymphatic system. Some immune cells have general or nonspecific functions. Others, such as T lymphocytes (T cells) and B lymphocytes (B cells), have specific functions. They recognize and are activated by specific antigens. B lymphocytes produce antibodies directed towards specific antigens, and cytotoxic T cells identify and kill cells containing the recognized antigen. Helper T cells release cytokines, including interferons and interleukins, which enhance immune activity at the site of the foreign-cell invasion by stimulating T cells to attack and B cells to produce more antibody. Cancer immunologists have high interest in these cell types.[5]

Eliciting the Immune Response

A vaccine is a preparation, usually administered subcutaneously, that creates a state of protection against a disease. Vaccines are created using carbohydrate and whole, or parts of, protein molecules from viruses or cells from bacteria, humans, or other animals. DNA or RNA may also be used to make vaccines. The molecules may contain a single antigen or several antigens.

The immune system responds by making antibodies against specific antigens present in the vaccine. Ideally, these antibodies are able to attack and destroy any substance identified by the body as foreign. Later, if the same substance is introduced anew, the circulating antibodies of the "vaccine-educated" immune system will recognize and destroy the foreign material. Some vaccines are long-lasting and protect an individual for years or even a lifetime.[6] Others have limited longevity and must be enhanced by periodic revaccination.

Advances in molecular biology and immunology have enhanced the opportunities to develop new vaccines. As new vaccines are developed and tested, they also are subject to review by a cooperative infrastructure of organizations convened by the National Institute of Allergy and Infectious Diseases. This consortium includes the National Cooperative Vaccine Development Groups, the HIV Vaccine Trials Network, the AIDS Vaccine Evaluation Group, and the National Cancer Institute of the National Institutes of Health.[1]

Preventive Cancer Vaccines

A cancer vaccine is generally considered an immunotherapy and is only preventive if it is administered before cancerous cells develop. The HPV and HBV vaccines, which are the only vaccines approved for cancer prevention, work by blocking infection with the causative agent, thereby preventing cancer in the vulnerable organs (cervix and liver, respectively). Other malignancies besides cervical and hepatic cancer that are associated with viruses include Burkitt's lymphoma and gastroadenocarcinoma, associated with Epstein Barr virus (EBV) type 1; nasopharyngeal carcinoma, associated with EBV type II; adult T cell leukemia, associated with HTLV-1; and Kaposi's sarcoma, associated with HHV-8.[2] Currently, no vaccines exist against the antigens associated with these viral agents.

Owing to factors inherent in the carcinogenesis process, cancer immunotherapy is easier when a causative agent can be targeted, as with cervical and liver cancers. HPV is the primary cause of cervical cancer. Early trials of the HPV vaccine (n = 1,500 young women) showed it to be 100% effective in preventing persistent HPV infection and low-grade cervical cytological abnormalities attributable to HPV 16 and HPV 18 strains of the virus.[7,8] These trials resulted in FDA approval in June 2006 of a quadrivalent HPV vaccine (against HPV types 6,11,16, and 18) for females aged 9 to 36 years (Gardasil).

Importantly, vaccination is only one approach toward reducing cancer risk. Other factors need to be considered. In terms of HPV infection, for example, there are 15 strains of HPV associated with cancer, 90% of HPV infections clear spontaneously within 2 years, the median age of cervical cancer diagnosis is 48 years, 60% of men are infected with HPV, and the HPV vaccine is not approved for males. There has also been controversy surrounding efforts to make vaccination of school-age girls mandatory.[9] (See Table 1.)

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