Immunotherapy
Encyclopedia
Immunotherapy is a medical term defined as the "treatment
of disease
by inducing, enhancing, or suppressing an immune response". 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
.
The active agents of immunotherapy are collectively called immunomodulators. They are a diverse array of recombinant, synthetic and natural preparations, often cytokines. Some of these substances, such as granulocyte colony-stimulating factor
(G-CSF), interferon
s, imiquimod
and cellular membrane fractions from bacteria
are already licensed for use in patients. Others including IL-2, IL-7, IL-12
, various chemokine
s, synthetic cytosine phosphate-guanosine (CpG), oligodeoxynucleotides and glucan
s are currently being investigated extensively in clinical and preclinical studies. Immunomodulatory regimens offer an attractive approach as they often have fewer side effects than existing drugs, including less potential for creating resistance in microbial diseases.
Cell based Immunotherapies are proven to be effective for some cancers. Immune effector cells such as lymphocyte
s, macrophage
s, dendritic cell
s, natural killer cell
s (NK Cell), cytotoxic T lymphocytes (CTL), etc., work together to defend the body against cancer by targeting abnormal antigens expressed on the surface of the tumor due to mutation.
to reject and destroy tumors. Dr William Coley used Coley's Toxins
in the late 1800s as crude immunotherapy with some success. Immuno cell therapy for cancer was first introduced by Rosenberg and his colleagues of National Institute of Health USA. In the late 80s, they published an article in which they reported a low tumor
regression
rate
(2.6–3.3%) in 1205 patients with metastatic cancer
who underwent different types of active specific immunotherapy (ASI), and suggested that immuno cell therapy along with specific chemotherapy
is the future of cancer immunotherapy. Initially Immunotherapy treatments involved administration of cytokines such as Interleukin. Thereafter the adverse effects of such intravenously administered cytokine
s
lead to the extraction of the lymphocytes from the blood and expanding in vitro against tumour antigen before injecting the cells with appropriate stimulatory cytokines. The cells will then specifically target and destroy the tumor expressing antigen against which they have been raised.
The concept of this treatment started in the US in 80s and fully fledged clinical treatments on a routine basis have been in practice in Japan since 1990. Randomized controlled studies in different cancers resulting in significant increase in survival and disease free period have been reported and its efficacy is enhanced by 20 – 30% when cell based immunotherapy is combined with other conventional treatment methods.
BCG
immunotherapy for early stage (non-invasive) bladder cancer
utilizes instillation of attenuated live bacteria
into the bladder
, and is effective in preventing recurrence in up to two thirds of cases. Topical immunotherapy utilizes an immune enhancement cream (imiquimod
) which is an interferon producer causing the patients own killer T cells to destroy wart
s, actinic keratoses, basal cell cancer, vaginal intraepithelial neoplasia
, squamous cell cancer, cutaneous lymphoma, and superficial malignant melanoma,. Injection immunotherapy uses mumps, candida the HPV vaccine or trichophytin antigen
injections to treat warts (HPV induced tumors). Lung cancer
has been demonstrated to potentially respond to immunotherapy
. Dendritic cells, a type of antigen presenting cell, are harvested from a patient. These cells are then either pulsed with an antigen or transfected with a viral vector
. Upon transfusion back into the patient these activated cells present tumour antigen to effector lymphocytes (CD4+ T cells, CD8+ T cells, and B cells). This initiates a cytotoxic response to occur against cells expressing tumour antigens (against which the adaptive response has now been primed). The Dendreon
cancer vaccine
Provenge is one example of this approach.
uses T cell-based cytotoxic responses to attack cancer cells. T cells that have a natural or genetically engineered reactivity to a patient's cancer are generated in vitro and then transferred back into the cancer patient. One study using autologous tumor-infiltrating lymphocytes was an effective treatment for patients with metastatic melanoma;. This can be achieved by taking T cells that are found with the tumor of the patient, which are trained to attack the cancerous cells. These T cells are referred to as tumor-infiltrating lymphocytes (TIL) are then encouraged to multiply in vitro using high concentrations of IL-2, anti-CD3 and allo-reactive feeder cells. These T cells are then transferred back into the patient along with exogenous administration of IL-2 to further boost their anti-cancer activity.
Thus far, a 51% objective response rate has been observed; and in some patients, tumors shrank to undetectable size.
The initial studies of adoptive cell transfer
using TIL, however, revealed that persistence of the transferred cells in vivo was too short. Before reinfusion, lymphodepletion of the recipient is required to eliminate regulatory T cells as well as normal endogenous lymphocytes that compete with the transferred cells for homeostatic cytokines. Lymphodepletion was made by total body irradiation prior to transfer of the expanded TIL. The trend for increasing survival as a function of increasing lymphodepletion was highly significant (P=0.007). Transferred cells expanded in vivo and persisted in the peripheral blood in many patients, sometimes achieving levels of 75% of all CD8+ T cells at 6–12 months after infusion.
Clinical trials based on adoptive cell transfer
of TILs for patients with metastatic melanoma are currently ongoing at the National Cancer Institute (Bethesda,MD,USA), MD Anderson Cancer Center (Houston,TX,USA), Sheba Medical Center (Tel Hashomer,Israel) and Herlev University Hospital (Herlev,Denmark)
Genetically engineered T cells are created by infecting patient's cells with a virus that contain a copy of a T cell receptor
(TCR) gene that is specialised to recognise tumour antigens. The virus is not able to reproduce within the cell however integrates into the human genome. This is beneficial as new TCR gene remains stable in the T-cell. A patient's own T cells are exposed to these viruses and then expanded non-specifically or stimulated using the genetically engineered TCR. The cells are then transferred back into the patient and ready to have an immune response against the tumour. Morgan et al. (2006) demonstrated that the adoptive cell transfer of lymphocytes transduced with retrovirus encoding TCRs that recognize a cancer antigen are able to mediate anti-tumour responses in patients with metastatic melanomas. This therapy has been demonstrated to result in objective clinical responses in patients with refractory stage IV cancer. The Surgery Branch of the National Cancer Institute (Bethesda, Maryland) is actively investigating this form of cancer treatment for patients suffering aggressive melanomas . The use of adoptive cell transfer with genetic engineered T cells is a promising new approach to the treatment of a variety of cancers.
In one case study, United States
doctors from the Clinical Research Division, led by Dr. Cassian Yee at Fred Hutchinson Cancer Research Center
in Seattle had successfully treated a patient with advanced skin cancer
by injecting the patient with immune cells cloned from his own immune system
. The patient was free from tumours within eight weeks of treatment. Dr. Cassian Yee described the research findings at The Cancer Research Institute International 2008 Symposia Series. http://www.cancerresearch.org/events/symposium/cancer-immunology-immunotherapy-2008/program-speakers.html. Responses, however, were not seen in other patients in this clinical trial. Larger trials are now under way. http://www.telegraph.co.uk/earth/main.jhtml?xml=/earth/2008/06/18/scicanc118.xml http://www.breitbart.com/article.php?id=080618212711.38ht6zq0&show_article=1
, involves activating the immune system
to respond to an infectious agent.
of transplanted
organs or cells.
is the process by which the body naturally does not launch an immune system attack on its own tissues. Immune tolerance therapies seeks to reset the immune system so that the body stops mistakenly attacking its own organs or cells in autoimmune disease
or accepts foreign tissue in organ transplant
ation. A brief treatment should then reduce or eliminate the need for life-long immunosuppression and the chances of attendant side effects, in the case of transplantation, or preserve the body's own function, at least in part, in cases of type 1 diabetes or other autoimmune disorders.
. While other allergy treatments (such as antihistamine
s or corticosteroids) treat only the symptoms of allergic disease, immunotherapy is the only available treatment that can modify the natural course of the allergic disease, by reducing sensitivity to allergen
s.
A three-to-five-year individually tailored regimen of injections may result in long-term benefits. Recent research suggests that patients who complete immunotherapy may continue to see benefits for years to come. Immunotherapy does not work for everyone and is only partly effective in some people, but it offers allergy sufferers the chance to eventually reduce or stop symptomatic/rescue medication.
The therapy is indicated for people who are extremely allergic or who cannot avoid specific allergen
s. For example, they may not be able to live a normal life and completely avoid pollen, dust mites, mold spores, pet dander, insect venom, and certain other common triggers of allergic reactions. Immunotherapy is generally not indicated for food or medicinal allergies. Immunotherapy is typically individually tailored and administered by an allergist (allergologist). Injection schedules are available in some healthcare systems and can be prescribed by family physicians. This therapy is particularly useful for people with allergic rhinitis
or asthma
.
The therapy is particularly likely to be successful if it begins early in life or soon after the allergy develops for the first time. Immunotherapy involves a series of injections (shots) given regularly for several years by a specialist in a hospital clinic. In the past, this was called a serum, but this is an incorrect name. Most allergists now call this mixture an allergy extract. The first shots contain very tiny amounts of the allergen or antigen to which you are allergic. With progressively increasing dosages over time, your body will adjust to the allergen and become less sensitive to it. This process is called desensitization. A recently approved sublingual tablet (Grazax), containing a grass pollen extract, is similarly effective, with few side effects, and can be self-administered at home, including by those patients who also suffer from allergic asthma, a condition which precludes the use of injection-based desensitization. To read more about this topic, see: allergy
and hyposensitization
.
ova (Trichuris suis) and Hookworm
(Necator americanus) for the treatment of certain immunological diseases and allergies means that these organisms must be classified as immuno-therapeutic agents. Helminthic therapy
is being investigated as a potentially highly effective treatment for the symptoms and or disease process in disorders such as relapsing remitting multiple sclerosis
Crohn’s
, allergies and asthma. The precise mechanism of how the helminths modulate the immune response, ensuring their survival in the host and incidentally effectively modulating autoimmune disease processes, is currently unknown. However, several broad mechanisms have been postulated, such as a re-polarisation of the Th1 / Th2 response, and modulation of dendritic cell function The helminths down regulate the pro-inflammatory Th1 cytokines, Interleukin-12 (IL-12), Interferon-Gamma (IFN-γ) and Tumour Necrosis Factor-Alpha (TNF-ά), while promoting the production of regulatory Th2 cytokines such as IL-10, IL-4, IL-5
and IL-13
.
That helminths modulate host immune response is proven, as the core assertion of the hygiene hypothesis
appears to have been, with the recent publication of a study demonstrating that co-evolution with helminths has shaped at least some of the genes associated with Interleukin
expression and immunological disorders, like Crohn's, ulcerative colitis
and Celiac Disease. Much of the research that has been published now indicates a key role, for what have been traditionally regarded as disease causing organisms,
Therapy
This is a list of types of therapy .* Adventure therapy* Animal-assisted therapy* Aquatic therapy* Aromatherapy* Art and dementia* Art therapy* Authentic Movement* Behavioral therapy* Bibliotherapy* Buteyko Method* Chemotherapy...
of disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
by inducing, enhancing, or suppressing an immune response". 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
Immunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
.
| Agent | Example |
|---|---|
| Interleukins | IL-2, IL-7 IL-7 IL-7 or IL 7 can refer to:* Interleukin 7* Illinois' 7th congressional district* Illinois Route 7... , IL-12 IL-12 IL-12 or IL 12 can refer to:Medicine* Interleukin 12Airplanes* Ilyushin Il-12Politics* Illinois' 12th congressional districtRoads* Illinois Route 12... |
| Cytokines | Interferon Interferon Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to... s, G-CSF, Imiquimod Imiquimod Imiquimod is a prescription medication that acts as an immune response modifier. It is marketed by Meda AB, Graceway Pharmaceuticals and iNova Pharmaceuticals under the trade names Aldara and Zyclara, and by Mochida as Beselna. It is also referred to as R-837.- History :The original FDA approval... |
| Chemokines | |
| Other | cytosine phosphate-guanosine, oligodeoxynucleotides, glucans |
The active agents of immunotherapy are collectively called immunomodulators. They are a diverse array of recombinant, synthetic and natural preparations, often cytokines. Some of these substances, such as granulocyte colony-stimulating factor
Granulocyte colony-stimulating factor
Granulocyte colony-stimulating factor is a colony-stimulating factor hormone. G-CSF is also known as colony-stimulating factor 3 ....
(G-CSF), interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
s, imiquimod
Imiquimod
Imiquimod is a prescription medication that acts as an immune response modifier. It is marketed by Meda AB, Graceway Pharmaceuticals and iNova Pharmaceuticals under the trade names Aldara and Zyclara, and by Mochida as Beselna. It is also referred to as R-837.- History :The original FDA approval...
and cellular membrane fractions from bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
are already licensed for use in patients. Others including IL-2, IL-7, IL-12
Interleukin 12
Interleukin 12 is an interleukin that is naturally produced by dendritic cells, macrophages and human B-lymphoblastoid cells in response to antigenic stimulation.-Gene and structure:...
, various chemokine
Chemokine
Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
s, synthetic cytosine phosphate-guanosine (CpG), oligodeoxynucleotides and glucan
Glucan
A glucan molecule is a polysaccharide of D-glucose monomers linked by glycosidic bonds.Many beta-glucans are medically important.-Types:The following are glucans:-Alpha:...
s are currently being investigated extensively in clinical and preclinical studies. Immunomodulatory regimens offer an attractive approach as they often have fewer side effects than existing drugs, including less potential for creating resistance in microbial diseases.
Cell based Immunotherapies are proven to be effective for some cancers. Immune effector cells such as lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s, macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s, dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
s, natural killer cell
Natural killer cell
Natural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses...
s (NK Cell), cytotoxic T lymphocytes (CTL), etc., work together to defend the body against cancer by targeting abnormal antigens expressed on the surface of the tumor due to mutation.
Cancer
Cancer immunotherapy attempts to stimulate the immune systemImmune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
to reject and destroy tumors. Dr William Coley used Coley's Toxins
Coley's Toxins
Coley's toxins is a mixture consisting of killed bacteria of species Streptococcus pyogenes and Serratia marcescens, named after William Coley, a surgical oncologist who developed the mixture in the late 19th century as a treatment for cancer.- History :Observations of...
in the late 1800s as crude immunotherapy with some success. Immuno cell therapy for cancer was first introduced by Rosenberg and his colleagues of National Institute of Health USA. In the late 80s, they published an article in which they reported a low tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
regression
Regression (medicine)
Regression in medicine is a characteristic of diseases to show lighter symptoms without completely disappearing. At a later point, symptoms may return. These symptoms are then called recidive....
rate
Rate
In mathematics, a rate is a ratio between two measurements, often with different units. If the unit or quantity in respect of which something is changing is not specified, usually the rate is per unit time. However, a rate of change can be specified per unit time, or per unit of length or mass or...
(2.6–3.3%) in 1205 patients with metastatic cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
who underwent different types of active specific immunotherapy (ASI), and suggested that immuno cell therapy along with specific chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
is the future of cancer immunotherapy. Initially Immunotherapy treatments involved administration of cytokines such as Interleukin. Thereafter the adverse effects of such intravenously administered cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s
lead to the extraction of the lymphocytes from the blood and expanding in vitro against tumour antigen before injecting the cells with appropriate stimulatory cytokines. The cells will then specifically target and destroy the tumor expressing antigen against which they have been raised.
The concept of this treatment started in the US in 80s and fully fledged clinical treatments on a routine basis have been in practice in Japan since 1990. Randomized controlled studies in different cancers resulting in significant increase in survival and disease free period have been reported and its efficacy is enhanced by 20 – 30% when cell based immunotherapy is combined with other conventional treatment methods.
BCG
Bacillus Calmette-Guérin
Bacillus Calmette-Guérin is a vaccine against tuberculosis that is prepared from a strain of the attenuated live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its virulence in humans by being specially subcultured in an artificial medium for 13 years, and also prepared from...
immunotherapy for early stage (non-invasive) bladder cancer
Bladder cancer
Bladder cancer is any of several types of malignant growths of the urinary bladder. It is a disease in which abnormal cells multiply without control in the bladder. The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis...
utilizes instillation of attenuated live bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
into the bladder
Bladder
Bladder usually refers to an anatomical hollow organBladder may also refer to:-Biology:* Urinary bladder in humans** Urinary bladder ** Bladder control; see Urinary incontinence** Artificial urinary bladder, in humans...
, and is effective in preventing recurrence in up to two thirds of cases. Topical immunotherapy utilizes an immune enhancement cream (imiquimod
Imiquimod
Imiquimod is a prescription medication that acts as an immune response modifier. It is marketed by Meda AB, Graceway Pharmaceuticals and iNova Pharmaceuticals under the trade names Aldara and Zyclara, and by Mochida as Beselna. It is also referred to as R-837.- History :The original FDA approval...
) which is an interferon producer causing the patients own killer T cells to destroy wart
Wart
A wart is generally a small, rough growth, typically on a human’s hands or feet but often other locations, that can resemble a cauliflower or a solid blister. They are caused by a viral infection, specifically by human papillomavirus 2 and 7. There are as many as 10 varieties of warts, the most...
s, actinic keratoses, basal cell cancer, vaginal intraepithelial neoplasia
Vaginal intraepithelial neoplasia
Vaginal intraepithelial neoplasia is a condition that describes premalignant histological findings in the vagina characterized by dysplastic changes.The disorder is rare and generally has no symptoms...
, squamous cell cancer, cutaneous lymphoma, and superficial malignant melanoma,. Injection immunotherapy uses mumps, candida the HPV vaccine or trichophytin antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
injections to treat warts (HPV induced tumors). Lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
has been demonstrated to potentially respond to immunotherapy
Dendritic cell based immunotherapy
Dendritic cells can be stimulated to activate a cytotoxic response towards an antigenAntigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
. Dendritic cells, a type of antigen presenting cell, are harvested from a patient. These cells are then either pulsed with an antigen or transfected with a viral vector
Viral vector
Viral vectors are a tool commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism or in cell culture . Viruses have evolved specialized molecular mechanisms to efficiently transport their genomes inside the cells they infect...
. Upon transfusion back into the patient these activated cells present tumour antigen to effector lymphocytes (CD4+ T cells, CD8+ T cells, and B cells). This initiates a cytotoxic response to occur against cells expressing tumour antigens (against which the adaptive response has now been primed). The Dendreon
Dendreon
Dendreon is a Seattle based biotechnology company. Its lead product, Provenge , is an immunotherapy for prostate cancer...
cancer vaccine
Cancer vaccine
The term cancer vaccine refers to a vaccine that either prevents infections with cancer-causing viruses, treats existing cancer or prevents the development of cancer in certain high risk individuals...
Provenge is one example of this approach.
T-cell adoptive transfer
Adoptive cell transferAdoptive cell transfer
Adoptive cell transfer is the passive transfer of cells, most commonly immune-derived cells, into a new recipient host with the goal of transferring the immunologic functionality and characteristics into the new host...
uses T cell-based cytotoxic responses to attack cancer cells. T cells that have a natural or genetically engineered reactivity to a patient's cancer are generated in vitro and then transferred back into the cancer patient. One study using autologous tumor-infiltrating lymphocytes was an effective treatment for patients with metastatic melanoma;. This can be achieved by taking T cells that are found with the tumor of the patient, which are trained to attack the cancerous cells. These T cells are referred to as tumor-infiltrating lymphocytes (TIL) are then encouraged to multiply in vitro using high concentrations of IL-2, anti-CD3 and allo-reactive feeder cells. These T cells are then transferred back into the patient along with exogenous administration of IL-2 to further boost their anti-cancer activity.
Thus far, a 51% objective response rate has been observed; and in some patients, tumors shrank to undetectable size.
The initial studies of adoptive cell transfer
Adoptive cell transfer
Adoptive cell transfer is the passive transfer of cells, most commonly immune-derived cells, into a new recipient host with the goal of transferring the immunologic functionality and characteristics into the new host...
using TIL, however, revealed that persistence of the transferred cells in vivo was too short. Before reinfusion, lymphodepletion of the recipient is required to eliminate regulatory T cells as well as normal endogenous lymphocytes that compete with the transferred cells for homeostatic cytokines. Lymphodepletion was made by total body irradiation prior to transfer of the expanded TIL. The trend for increasing survival as a function of increasing lymphodepletion was highly significant (P=0.007). Transferred cells expanded in vivo and persisted in the peripheral blood in many patients, sometimes achieving levels of 75% of all CD8+ T cells at 6–12 months after infusion.
Clinical trials based on adoptive cell transfer
Adoptive cell transfer
Adoptive cell transfer is the passive transfer of cells, most commonly immune-derived cells, into a new recipient host with the goal of transferring the immunologic functionality and characteristics into the new host...
of TILs for patients with metastatic melanoma are currently ongoing at the National Cancer Institute (Bethesda,MD,USA), MD Anderson Cancer Center (Houston,TX,USA), Sheba Medical Center (Tel Hashomer,Israel) and Herlev University Hospital (Herlev,Denmark)
Genetically Engineered T cells
Genetically engineered T cells are created by infecting patient's cells with a virus that contain a copy of a T cell receptor
T cell receptor
The T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is responsible for recognizing antigens bound to major histocompatibility complex molecules...
(TCR) gene that is specialised to recognise tumour antigens. The virus is not able to reproduce within the cell however integrates into the human genome. This is beneficial as new TCR gene remains stable in the T-cell. A patient's own T cells are exposed to these viruses and then expanded non-specifically or stimulated using the genetically engineered TCR. The cells are then transferred back into the patient and ready to have an immune response against the tumour. Morgan et al. (2006) demonstrated that the adoptive cell transfer of lymphocytes transduced with retrovirus encoding TCRs that recognize a cancer antigen are able to mediate anti-tumour responses in patients with metastatic melanomas. This therapy has been demonstrated to result in objective clinical responses in patients with refractory stage IV cancer. The Surgery Branch of the National Cancer Institute (Bethesda, Maryland) is actively investigating this form of cancer treatment for patients suffering aggressive melanomas . The use of adoptive cell transfer with genetic engineered T cells is a promising new approach to the treatment of a variety of cancers.
In one case study, United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
doctors from the Clinical Research Division, led by Dr. Cassian Yee at Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center
The Fred Hutchinson Cancer Research Center, is one of the world’s leading cancer research institutes...
in Seattle had successfully treated a patient with advanced skin cancer
Skin cancer
Skin neoplasms are skin growths with differing causes and varying degrees of malignancy. The three most common malignant skin cancers are basal cell cancer, squamous cell cancer, and melanoma, each of which is named after the type of skin cell from which it arises...
by injecting the patient with immune cells cloned from his own immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
. The patient was free from tumours within eight weeks of treatment. Dr. Cassian Yee described the research findings at The Cancer Research Institute International 2008 Symposia Series. http://www.cancerresearch.org/events/symposium/cancer-immunology-immunotherapy-2008/program-speakers.html. Responses, however, were not seen in other patients in this clinical trial. Larger trials are now under way. http://www.telegraph.co.uk/earth/main.jhtml?xml=/earth/2008/06/18/scicanc118.xml http://www.breitbart.com/article.php?id=080618212711.38ht6zq0&show_article=1
Immune Recovery
The potential use of immunotherapy to restore the immune system of patients with immune deficiencies as result of infection or chemotherapy. For example cytokines have been tested in clinical trials interleukin-7 has been in clinical trials for HIV and cancer patients. In addition, interleukin-2 has also been tested in HIV patients.Vaccination
Anti-microbial immunotherapy, which includes vaccinationVaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
, involves activating the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
to respond to an infectious agent.
Suppression immunotherapies
Immune suppression dampens an abnormal immune response in autoimmune diseases or reduces a normal immune response to prevent rejectionTransplant rejection
Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after...
of transplanted
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
organs or cells.
Immune tolerance
Immune toleranceImmune tolerance
Immune tolerance or immunological tolerance is the process by which the immune system does not attack an antigen. It can be either 'natural' or 'self tolerance', in which the body does not mount an immune response to self antigens, or 'induced tolerance', in which tolerance to external antigens can...
is the process by which the body naturally does not launch an immune system attack on its own tissues. Immune tolerance therapies seeks to reset the immune system so that the body stops mistakenly attacking its own organs or cells in autoimmune disease
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
or accepts foreign tissue in organ transplant
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
ation. A brief treatment should then reduce or eliminate the need for life-long immunosuppression and the chances of attendant side effects, in the case of transplantation, or preserve the body's own function, at least in part, in cases of type 1 diabetes or other autoimmune disorders.
Allergies
Immunotherapy is also used to treat allergiesAllergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
. While other allergy treatments (such as antihistamine
Antihistamine
An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...
s or corticosteroids) treat only the symptoms of allergic disease, immunotherapy is the only available treatment that can modify the natural course of the allergic disease, by reducing sensitivity to allergen
Allergen
An allergen is any substance that can cause an allergy. In technical terms, an allergen is a non-parasitic antigen capable of stimulating a type-I hypersensitivity reaction in atopic individuals....
s.
A three-to-five-year individually tailored regimen of injections may result in long-term benefits. Recent research suggests that patients who complete immunotherapy may continue to see benefits for years to come. Immunotherapy does not work for everyone and is only partly effective in some people, but it offers allergy sufferers the chance to eventually reduce or stop symptomatic/rescue medication.
The therapy is indicated for people who are extremely allergic or who cannot avoid specific allergen
Allergen
An allergen is any substance that can cause an allergy. In technical terms, an allergen is a non-parasitic antigen capable of stimulating a type-I hypersensitivity reaction in atopic individuals....
s. For example, they may not be able to live a normal life and completely avoid pollen, dust mites, mold spores, pet dander, insect venom, and certain other common triggers of allergic reactions. Immunotherapy is generally not indicated for food or medicinal allergies. Immunotherapy is typically individually tailored and administered by an allergist (allergologist). Injection schedules are available in some healthcare systems and can be prescribed by family physicians. This therapy is particularly useful for people with allergic rhinitis
Allergic rhinitis
Allergic rhinitis, also known as pollenosis or hay fever, is an allergic inflammation of the nasal airways.It occurs when an allergen, such as pollen, dust or animal dander is inhaled by an individual with a sensitized immune system...
or asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
.
The therapy is particularly likely to be successful if it begins early in life or soon after the allergy develops for the first time. Immunotherapy involves a series of injections (shots) given regularly for several years by a specialist in a hospital clinic. In the past, this was called a serum, but this is an incorrect name. Most allergists now call this mixture an allergy extract. The first shots contain very tiny amounts of the allergen or antigen to which you are allergic. With progressively increasing dosages over time, your body will adjust to the allergen and become less sensitive to it. This process is called desensitization. A recently approved sublingual tablet (Grazax), containing a grass pollen extract, is similarly effective, with few side effects, and can be self-administered at home, including by those patients who also suffer from allergic asthma, a condition which precludes the use of injection-based desensitization. To read more about this topic, see: allergy
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
and hyposensitization
Hyposensitization
Allergen immunotherapy is a form of immunotherapy for allergic disorders in which the patient is vaccinated with increasingly larger doses of an allergen with the aim of inducing immunologic...
.
Helminthic therapies
Recent research into the clinical effectiveness of WhipwormWhipworm
The human tapworm is a roundworm, which causes trichuriasis when it infects a human large intestine. The name whipworm refers to the shape of the worm; they look like whips with wider "handles" at the posterior end.-Life cycle:The female T. trichiura produces 2,000–10,000 single celled eggs per day...
ova (Trichuris suis) and Hookworm
Hookworm
The hookworm is a parasitic nematode that lives in the small intestine of its host, which may be a mammal such as a dog, cat, or human. Two species of hookworms commonly infect humans, Ancylostoma duodenale and Necator americanus. A. duodenale predominates in the Middle East, North Africa, India...
(Necator americanus) for the treatment of certain immunological diseases and allergies means that these organisms must be classified as immuno-therapeutic agents. Helminthic therapy
Helminthic therapy
Helminthic therapy, a type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the ova of a helminth. Helminths are parasitic worms such as hookworms and whipworms....
is being investigated as a potentially highly effective treatment for the symptoms and or disease process in disorders such as relapsing remitting multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
Crohn’s
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
, allergies and asthma. The precise mechanism of how the helminths modulate the immune response, ensuring their survival in the host and incidentally effectively modulating autoimmune disease processes, is currently unknown. However, several broad mechanisms have been postulated, such as a re-polarisation of the Th1 / Th2 response, and modulation of dendritic cell function The helminths down regulate the pro-inflammatory Th1 cytokines, Interleukin-12 (IL-12), Interferon-Gamma (IFN-γ) and Tumour Necrosis Factor-Alpha (TNF-ά), while promoting the production of regulatory Th2 cytokines such as IL-10, IL-4, IL-5
IL-5
IL 5 or IL-5 may refer to:* Interleukin 5* Illinois' 5th congressional district* Illinois Route 5...
and IL-13
IL-13
IL-13 or IL 13 can refer to:* Interleukin 13* Illinois' 13th congressional district* Illinois Route 13...
.
That helminths modulate host immune response is proven, as the core assertion of the hygiene hypothesis
Hygiene hypothesis
In medicine, the Hygiene Hypothesis states that a lack of early childhood exposure to infectious agents, symbiotic microorganisms , and parasites increases susceptibility to allergic diseases by suppressing natural development of the immune system...
appears to have been, with the recent publication of a study demonstrating that co-evolution with helminths has shaped at least some of the genes associated with Interleukin
Interleukin
Interleukins are a group of cytokines that were first seen to be expressed by white blood cells . The term interleukin derives from "as a means of communication", and "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes"...
expression and immunological disorders, like Crohn's, ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
and Celiac Disease. Much of the research that has been published now indicates a key role, for what have been traditionally regarded as disease causing organisms,
External links
- "Cancer Miracles" Forbes article
- International Society for Biological Therapy of Cancer
- Cancer Research Institute Annual International Cancer Immunotherapy Symposia Series
- Immunotherapy for Cancer in India
- Autologous Immune Enhancement Therapy (AIET)in India
- Autologous Immune Enhancement Therapy (AIET) in Malaysia