What are cancer vaccines?
Cancer vaccines are either preventive or therapeutic. Preventive, or prophylactic, vaccines prevent cancer from developing in healthy persons. Therapeutic, or treatment, vaccines treat existing cancer by strengthening the body’s immune response against the malignancy.
Vaccines are commonly known for their benefits in preventing or fighting infectious diseases such as polio, tetanus, or measles. Vaccines, as a form of immunotherapy, promote immunity, the body’s defense against pathogens and injured or abnormal cells, such as cancer cells. The immune system, which can deliver its effector components to different locations in the body, is such a highly specific system that it can isolate one cancer cell from a vast amount of other healthy cells and destroy that cancer cell.
Utilizing basic principles of infectious disease vaccines, a new type of vaccine is being developed to target one of the most critical public health concerns: cancer. Although some advances have been made, cancer is still the leading cause of death in persons younger than age eighty-five years in the United States.
Cancer is a group of diseases characterized by abnormal and uncontrolled cell growth, invasion, and sometimes metastasis. In a healthy body, cells grow, die, and are replaced in a regulated fashion. Damage or change in the genetic material of cells by internal or environmental factors sometimes results in immortal cells, which continue to multiply until a mass of cancer cells, or a tumor, develops. Most cancer-related deaths are caused by metastasis, in which malignant cells make their way into the bloodstream and establish colonies in other parts of the body. Cancer immunotherapy manipulates the immune system to overcome self-tolerance and to recognize cancer cells.
Like the traditional vaccines that present inactivated, attenuated, or subunit pathogens to the immune system, cancer vaccines present the right cancer antigen in combination with the right adjuvant to generate the right type of immune response. This response, whether humoral or cellular, ideally should destroy the cancer only and leave healthy cells untouched. Cancer cells are different from normal healthy cells. As such, they are recognized by the immune system as being different. Proteins expressed by cancer cells are different from normal proteins or are absent in normal differentiated cells. These proteins can be immunogenic when presented in the context of a cancer vaccine.
The vaccine is made from cancer-specific proteins or proteins that are found predominantly in cancer cells. Because of the associated immunologic memory, the risk of recurrence is reduced compared with traditional treatments. Rather than compromise the immune system, as many chemotherapy treatments do, cancer vaccines train the immune system to target those specific malignant cells. Consequently, some cancer vaccines are safer and do not have the traditional side effects associated with chemotherapy or radiation therapy. Depending on the specific vaccine, cancer vaccines might be stand-alone therapies or may be used with other conventional cancer therapies.
Every cancer, and its vaccine, is different. Personalized medicine is critical to the development of vaccines that must be tailor-made to each person.
Cancer vaccines are characterized as either active or passive immunotherapies. While the active type aims to elicit the host immune system to fight the disease, the passive type does not depend on the body’s defenses to start the attack. Instead, it uses administered medicines (antibodies or T cell therapy) to destroy the tumor. Passive immunotherapy has no immunologic memory associated with the treatment. Any of these therapies can be targeted to one type of tumor cell or antigen (specific immunotherapies) or can generally stimulate the immune system (nonspecific immunotherapies).
Cancer vaccines are either therapeutic or preventive. Therapeutic vaccines treat persons at early stages of the disease or with minimal residual disease after removal of the main tumor. In some cases, advanced disease may be treated with a vaccine. Preventive vaccines include the human papillomavirus (HPV) vaccine, which can prevent cervical, vaginal, and vulvar cancers. The hepatitis B virus (HBV) vaccine lowers the risk of developing liver cancer. The Helicobacter pylori vaccine targets the bacterium H. pylori, which is associated with stomach cancer. Hence, the HPV, HBV, and H. pylori vaccines do not target cancer cells; rather, they are specific to the viruses or bacteria that give rise to these cancers.
Cancer vaccines target malignancies such as melanoma, leukemia, and non-Hodgkin’s lymphoma, and cancers of the lung, breast, kidney, ovary, pancreas, prostate, and colorectal area. The unique complex strategies used in cancer vaccine design depend on various considerations particular to the specific cancer process, the optimum level of immunity that can potentially be achieved, and a person’s health status.
In whole cancer-cell vaccines, cancer cells are irradiated before they are returned to the treated person’s body through injection. These vaccines contain thousands of potential antigens expressed in the whole tumor. Antigen vaccines, however, use only one antigen (or a few), whereas peptide vaccines present short fragments of the tumor protein.
Dendritic cell vaccines use specialized antigen-presenting cells that are efficient in presenting tumor antigens and tumor peptides to the immune system. Dendritic cells break down cancer proteins into small fragments and then present these antigens to T cells, thus improving immunologic antigen recognition and, eventually, cancer destruction. Nucleic acid vaccines use the genetic code that codes for cancer protein antigens so that the host cells make the cancer antigen continuously while keeping the immune response stimulated and strong.
Viral and bacterial, vector-based, vaccines can deliver antigens or genes encoding the tumor proteins or peptides to make the host’s immune system more apt to respond. Because bacterial and viral components on these vector vaccines represent pathogen danger signals, they may trigger additional immune responses that might benefit the overall response, making it more robust and longer lasting.
Anti-idiotype vaccines can act passively against B-cell lymphomas or actively by mimicking cancer antigens. In the latter case, these vaccines work through antibody cascades. Some of these vaccines contain adjuvants to amplify either the humoral or the cell-mediated (or both) immune responses to an antigen and break self-tolerance. Adjuvants have been developed to enhance immunogenicity when mixed with proteins, peptides, or deoxyribonucleic acid (DNA).Tumor peptide-MHC (major histocompatibility complex) complexes are important for the recognition of tumor cells by the immune system because tumor peptides are recognized only if they are joined to the MHC complex. Cytotoxic T cells are the killer cells that recognize the peptide-MHC complexes on the tumor cells and destroy the cancer cells.
Cancer vaccines have the potential to treat cancers in line with treatments such as surgery or radiation therapy. Cancer vaccines are mostly experimental, although some have already entered the drug market after receiving U.S. Food and Drug Administration approval. Some vaccines have shown promise in clinical trials, while others have advanced through late-stage clinical studies.
Using cancer vaccines after the removal of the main tumor by traditional means helps lead the body’s own immune system to destroy any remaining cancer cells and to target metastasis. Immunotherapy has the potential to strengthen the body’s natural defenses, despite cancers that might have already developed, and it can prevent new growth of existing cancers, hamper recurrence of treated cancers, and destroy cancer cells not previously eliminated by other treatments.
When cancer is controlled or cured, cachexia usually stops. During cachexia, there is wasting of adipose and skeletal muscle. Persons with pancreatic and gastric cancer, for example, suffer from acute cachexia. Those with cachexia suffer from poor functional performance, depressed chemotherapy response, and greater mortality. Therefore, the success of cancer vaccine development may benefit persons with cachexia enormously.
Immunotherapies themselves are costly, but in the long term, they reduce overall medical costs by reducing fees for patient care, management, hospitalization, and death. The pursuit and development of safe and effective cancer vaccines can greatly benefit immunologists, oncologists, molecular biologists, chemists, public health workers, and society in general. Above all, they help persons with cancer.
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Jemal, A., et al. “Cancer Statistics, 2010.” CA: A Cancer Journal for Clinicians 60, no. 5 (2010): 277-300. This clinical report examines cancer incidence, mortality, and survival based on incidence data.
Murphy, J. F. “Trends in Cancer Immunotherapy.” Clinical Medicine Insights: Oncology 4 (July 14, 2010): 67-80. Discusses the attempts of cancer immunotherapy to redirect the power and specificity of the immune system toward effectively and safely treating malignancy.
Plotkin, Stanley A., Walter A. Orenstein, and Paul A. Offit. Vaccines. 5th ed. Philadelphia: Saunders/Elsevier, 2008. A comprehensive vaccination textbook covering the topics of development, production, safety and efficacy, morbidity, and mortality.
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Rosenberg, S. A., J. C. Yang, and N. P. Restifo. “Cancer Immunotherapy: Moving Beyond Current Vaccines.” Nature Medicine 10, no. 9 (2004): 909-915. Review of a cancer vaccine trial that highlights secondary strategies that facilitate cancer regression in preclinical and clinical models.
Schlom, J., P. M. Arlen, and J. L. Gulley. “Cancer Vaccines: Moving Beyond Current Paradigms.” Clinical Cancer Research 13, no. 1 (2007): 3776-3782. Reviews several different cancer-vaccine clinical trials and respective patient response and survival outcomes.
The Scientist.com. “Immune System Versus Cancer.” Available at http://www.the-scientist.com/2009/11/1/36/1. Article that underscores the role of the immune system in cancer within the context of immune surveillance.
Sonpavde, G., et al. “Emerging Vaccine Therapy Approaches for Prostate Cancer.” Reviews in Urology 12, no. 1 (2010): 25-34. Explores different prostate vaccine approaches with selecting proper patient populations, discovering optimal doses, and routes of administration for better outcomes.