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Heat Shock Proteins: The Next Stage in Immunotherapy for Cancer Treatment
Basic Cancer Information
According to the American Cancer Society: “This year about 570,280 Americans are expected to die of cancer, more than 1,500 people a day. Cancer is the second leading cause of death in the US, exceeded only by heart disease. In the US, cancer causes 1 of every 4 deaths” (http://www.cancer.org/downloads/STT/CAFF2005f4PWSecured.pdf). The estimated number of new cases of cancer for all disease sites is 1,372,910 for 2005 alone, and that is still only in the United States. These statistics show how crucial finding an effective and efficient treatment for cancer is.
Cancer is the rapid growth and spread of irregular cells that can be caused by external factors, such as tobacco, exposure to harmful chemicals, and radiation, or internal factors, such as mutations, hormones, or problems with the body’s immune system. Depending on the type and stage, cancer can be treated with surgery, chemotherapy, radiation therapy, immunotherapy, hormones, or a combination of these treatments (http://www.cancer.org/downloads/STT/CAFF2005f4PWSecured.pdf).
Cancer Vaccines- What are they? How do they work?
Immunotherapy, or biological therapy, is a growing field in terms of cancer treatment, and can be defined as: “A type of treatment that mobilizes the body’s immune system to fight cancer. The therapy mainly consists of stimulating the immune system to help it do its job more effectively” (http://www.clevelandclinic.org/cancer/general/glossary/i.htm). Immunotherapy is becoming a more popular method to treat cancer in the form of vaccines, whether for cancers that have already been diagnosed (therapeutic vaccines), or for the prevention of the development of cancer in the future (prophylactic vaccines) (http://www.cancer.gov/cancertopics/factsheet/cancervaccine).
Cancer vaccines are created by removing cancer cells from the body and killing the cells (usually with radiation) in order to prevent more tumors from growing when the vaccine is reintroduced into the body. Doctors can then alter the cells by using chemicals or adding genes. The newly created vaccine, once injected under the skin (subcutaneously), stimulates a response from the immune system, causing it to attack cells that appear similar to those used in the vaccine. (http://www.cancer.org/docroot/ETO/content/ETO_1_4X_Cancer_Vaccines_Active_Specific_Immunotherapies.asp?sitearea=ETO)
Antigens are the substances that actually stimulate the immune system in order to produce antibodies‑which are highly specific molecules in the blood that help track down and destroy toxins. Antigens are often foreign to the body, such as invading bacteria or viruses (http://my.webmd.com/content/article/5/1680_50211.htm). Cancer cell antigens are used in treatment vaccines, and, in the case of cancer, believed to track down abnormal cells and destroy them as mentioned above.
There are two classifications for cancer vaccines: autologous vaccines are made up of the patient’s own cells and allogeneic vaccines are created using one person’s cells while the vaccination is given to a different patient. (http://www.cancer.org/docroot/ETO/content/ETO_1_4X_Cancer_Vaccines_Active_Specific_Immunotherapies.asp?sitearea=ETO)
Heat Shock Proteins
Heat Shock Proteins, or HSPs, are an example of cancer cell antigens. HSPs “are produced in cells in response to heat, low sugar levels and other stress signals. Besides protecting against stress, these molecules are also involved in the proper processing, folding, and assembling of proteins within cells” (http://www.antigenics.com/products/tech/hsp/). ). Because of their role of ensuring that proteins are put together correctly, HSPs are often referred to as “chaperones.” They exist in virtually every type of cell, as well as every type of living being, and can also assist in transport and the presentation of peptides, which are the building blocks of proteins, at the surface of cells so the immune system is able to identify problematic cells (
When HSPs come across portions of tumors known as epitopes, which are protein pieces that serve as identifiers on cancer cells, the HSPs can “absorb” the fragments allowing them to be analyzed by the immune system. This can lead to the ability of the body to recognize the diseased cells. Cytotoxic T-Lymphocytes then destroy the cancer cells that generated the portions originally absorbed by the HSPs, hopefully killing the tumor (http://www.cancerresearch.org/release3.html). Cytotoxic T-Lymphocytes are “immune system cells that can destroy cancer cells and cells infected with viruses, fungi, or certain bacteria” (http://my.webmd.com/content/article/5/1680_50211.htm). While HSPs perform many crucial functions when inside the cell, if they are detected outside, it serves as a warning signal to the immune system, indicating that the cell was seriously diseased and causing it to burst and die in a process known as necrosis (http://www.antigenics.com/products/tech/hsp/).
HSPs are believed to be very beneficial for multiple reasons, including (1)the fact that large doses of HSP vaccines are not needed in order for the treatment to be effective, and (2)adjuvant therapy, meaning additional treatment such as chemotherapy or radiation therapy are not necessarily needed to generate a response from the immune system (http://www.cancerresearch.org/release3.html).
Both the American Cancer Society and The National Cancer Institute recognize the growing potential of HSPs and cancer vaccinations as both a treatment method and preventative method. According to the National Cancer Institute, it is believed that HSP vaccines may help in treating a wide range of cancers, including liver, skin, colon, lung, lymphoma and prostate (http://www.cancer.gov/cancertopics/factsheet/cancervaccine). However, pharmaceutical companies such as Antigenics, Inc. are also contributing to the promotion of vaccines.
What does the Research Say?
The majority of scientific journals with articles relating to the use of Heat Shock Proteins for cancer vaccinations found the current data to be very promising. In fact, many reiterated not only data, but processes and explanations of methods mentioned on the websites for both the American Cancer Society and the National Cancer Institute.
According to early Heat Shock Protein-peptide complexes (HSP-PC) studies in mice, the vaccines were effective in a multitude of cancers with a variety of origins, and also reduced the amount of metastasis, or spread of cancer (Ménoret and Chandawarkar, 1998). Pilot studies in humans indicated the promise associated with the use of immunotherapy when confirming its safety, efficacy, manufacturability, and ethical acceptability of the treatment (Ménoret and Chandawarkar, 1998). Because HSPs have shown strong immunological function, they will most likely be able to aid in cancer treatment in the form of vaccinations in the near future (Castelli et al., 2003).
However, each article also pointed to the fact that more research is needed in order to perfect the process and find all possible adverse events (negative side effects). As Bei, et al. stated: “There is a desperate need for well-designed clinical studies. Thus far, it is clear that customized HSP vaccination approach is feasible and relatively nontoxic. However, we have a long way to go before we know precisely how to use these remarkable molecules for battles against cancers” (2002).
The question of safety is always important when discussing new drugs or therapies, and that is no different with cancer vaccines. Luckily, the use of autologous treatment allows for a majority of the risk factors to be avoided because material from the patient’s own body is being used. Most patients reported “transient hot flashes related to the injection that wore out soon thereafter” (Ménoret and Chandawarkar, 1998) as side effects from the treatment. Nencioni, et al. stated: “The clinical studies performed so far have demonstrated that anticancer vaccine formulations can generally be safely administered without significant side effects, except for some cases of vitiligo observed in melanoma patients….However, the results of these studies need to be confirmed and the types of malignancies as well as the clinical settings for which specific immunotherapy may be beneficial need to be identified” (2004).
Medical advances in relation to cancer prevention and treatment are becoming more and more abundant, with severe side effects, such as those commonly associated with chemotherapy and radiation therapy, being minimized with every discovery. Heat Shock Protein Cancer Vaccines are one of such advances. There is a wealth of information on the internet relating to this type of treatment and, fortunately, the information seemed to be not only accurate, but positive as well in terms of the effectiveness and efficiency of HSP vaccines. However, as with any other major medical discovery, there is still a long way to go in terms of learning all the “ins and outs” of this type of treatment, according to scientific journals. Yet each of these scientific journals did emphasize the fact that the use of immunology and cancer vaccines is not too far in the future, for clinical trials that have already been performed in mice and humans have shown very promising results. It should not be too long before we start to see treatments such as cancer vaccines, both prophylactic and treatment oriented, as common as radiation therapy and chemotherapy.
American Cancer Soceity. “Cancer Facts & Figures 2005.” http://www.cancer.org/downloads/STT/CAFF2005f4PWSecured.pdf
American Cancer Society. “Cancer Vaccines.” http://www.cancer.org/docroot/ETO/content/ETO_1_4X_Cancer_Vaccines_Active_Specific_Immunotherapies.asp?sitearea=ETO
Antigenics. “Heat Shock Proteins: Basics.” http://www.antigenics.com/products/tech/hsp/
Cancer Research Institute. “Heat Shock Proteins: New Avenue to Cancer Vaccines.” http://www.cancerresearch.org/release3.html
National Cancer Institute. “Cancer Vaccine Fact Sheet.” http://www.cancer.gov/cancertopics/factsheet/cancervaccine
The Cleveland Clinic. “Glossary of Cancer Terms.” http://www.clevelandclinic.org/cancer/general/glossary/
WebMDHealth. “HIV Vaccine Glossary.” http://my.webmd.com/content/article/5/1680_50211.htm
Bei , L., DeFilippo, A. M., Zihai, L. (2002). “Overcoming Immune Tolerance to Cancer by Heat Shock Protein Vaccines.” Molecular Cacner Therapeutics vol 1, 1147-1151.
Castelli, C., Rivoltini, L., Rini, F., Belli, F., Testori, A., Maio, M., et al. (2003). “Heat shock proteins: biological functions and clinical application as personalized vaccines for human cancers. Cancer Immunology Immunotherapy 53, 227-223.
Ménoret, A. & Chandawarkar, R. (1998). “Heat-Shock Protein-Based Anticancer Immunotherapy: An Idea Whose Time Has Come.” Seminars in Oncology Vol 25, No 6, 654-660.
Nencioni, A., Grünebach, F., Patrone, F., & Brossart, P. (2004). “Anticancer vaccination strategies.” Annals of Oncology 13, iv153-iv160.
Photo 1: http://www.cedars-sinai.edu/3986.htm
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