Immunotherapy, in medicine, refers to an array of treatment strategies based upon the concept of modulating the immune system to achieve a prophylactic and/or therapeutic goal. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor Prophylaxis ( Greek "προφυλάσσω" to guard or prevent beforehand) is any medical or Public health procedure whose purpose Immunosuppression involves an act that reduces the activation or Efficacy of the Immune system.
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Activation
Cancer
Cancer immunotherapy attempts to stimulate the immune system to reject and destroy tumors. Cancer immunotherapy is the use of the Immune system to reject Cancer. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor 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. Bacillus Calmette-Guérin (or Bacille Calmette-Guérin, BCG) is a vaccine against Tuberculosis that is prepared from a strain of the attenuated Bladder cancer refers to any of several types of malignant growths of the Urinary bladder. Topical immunotherapy utilizes an immune enhancement cream (imiquimod) which is an interferon producer causing the patients own killer T cells to destroy warts, actinic keratoses, basal cell cancer, squamous cell cancer, cutaneous lymphoma, and superficial malignant melanoma. Imiquimod ( INN) is a prescription medication that acts as an immune response modifier Injection immunotherapy uses mumps, candida or trichophytin antigen injections to treat warts (HPV induced tumors).
Dendritic cell based immunotherapy
This utilizes dendritic cells to activate a cytotoxic response towards an antigen. Dendritic cells (DCs are Immune cells and form part of the Mammalian Immune system. Cytotoxicity is the quality of being toxic to cells Examples of toxic agents are a Chemical substance, an Immune cell or some types of Venom An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response Dendritic cells, an antigen presenting cell, are harvested from a patient. See also Antigen presentation An antigen-presenting cell ( APC) or accessory cell is a cell that displays foreign Antigen complexed These cells are then either pulsed with an antigen or transfected with a 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 The activated dendritic cells are then placed back into the patient; these cells then present the antigens to effector lymphocytes (CD4+ T cells, CD8+ T cells, and in specialized dendritic cells, B cells also). This initiates a cytotoxic response to occur against these antigens and anything that may present these antigens. One use for this therapy is in cancer immunotherapy. Tumor Antigens are presented to dendritic cells, which cause the immune system to target these antigens, which are often expressed on cancerous cells.
T cell based adoptive immunotherapy
This therapy uses T cell-based cytotoxic responses to attack cancer. In brief, T cells that have a natural or genetically engineered reactivity to a patients' cancer are expanded in vitro using a variety of means and then adoptively transferred into a cancer patient. T cells with a natural occurring reactivity to a patient’s cancer can be found infiltrated in the patients' own tumors. The tumor is harvested, and these tumor infiltrating lymphocytes (TIL) are expanded in vitro using high concentrations of interluekin-2 (IL-2), anti-CD3 and allo-reactive feeders. These T cells are then transferred back into the patient along with exogenous administration of IL-2. Thus far, a 51% objective response rate has been observed; in some patients, tumors shrank to indetectable size. In the case of engineered T cells, T cell receptors (TCR) that have been identified to have reactivity against tumor associated antigens are cloned into a replication incompetent virus that is capable of genomic integration. A patients own lymphocytes are exposed to these viruses and then expanded non-specifically or stimulated using the engineered TCR. The cells are then transferred back into the patient. 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.
Vaccination
Anti-microbial immunotherapy, which includes vaccination, involves activating the immune system to respond to an infectious agent. An antimicrobial is a substance that kills or inhibits the growth of Microbes such as Bacteria, Fungi, or Viruses. Vaccination is the administration of Antigenic material (the Vaccine) to produce immunity to a disease An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor
Suppression
Immune suppression dampens an abnormal immune response in autoimmune diseases or reduces a normal immune response to prevent rejection of transplanted organs or cells. Immunosuppression involves an act that reduces the activation or Efficacy of the Immune system. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor Transplant rejection occurs when a transplanted organ or tissue fails to be accepted by the body of the transplant recipient
Immune tolerance
Immune tolerance is the process by which the body naturally does not launch an immune system attack on its own tissues. Immune or immunological tolerance is the process by which the Immune system does not attack an Antigen. 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 transplantation. Autoimmune diseases arise from an overactive Immune response of the body against substances and tissues normally present in the body [1] 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 allergies. Hyposensitization (or allergy desensitization) is a form of Immunotherapy in which the patient is Vaccinated with progressively larger doses of an Allergy is a disorder of the Immune system often also referred to as Atopy. While other allergy treatments (such as antihistamines 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 allergens. A histamine antagonist is an agent which serves to inhibit the release or action of Histamine. Corticosteroids are a class of Steroid hormones that are produced in the Adrenal cortex. An allergen is a nonparasitic Antigen capable of stimulating a Type-I hypersensitivity reaction in atopic individuals
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. [2] 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 allergens. An allergen is a nonparasitic Antigen capable of stimulating a Type-I hypersensitivity reaction in atopic individuals 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. Hay Fever is a comic play written by Noel Coward in 1924 and first produced in 1925 with Marie Tempest as the first Judith Bliss Asthma is a chronic Condition involving the Respiratory system in which the airways occasionally constrict become inflamed, and are
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. Allergy is a disorder of the Immune system often also referred to as Atopy. Hyposensitization (or allergy desensitization) is a form of Immunotherapy in which the patient is Vaccinated with progressively larger doses of an
Societies
International Society for Biological Therapy of Cancer (iSBTc). The International Society for Biological Therapy of Cancer (iSBTc) is a 501 (c)(3) non-profit society of medical professionals. The iSBTc membership is over 500 of the most influential leaders in the field of biological therapy and includes academicians, government representatives, industry leaders, senior investigators, and students. The core purpose of the iSBTc is to improve cancer patient outcomes by advancing the development and application of biological therapy. The society’s web site is: [1]
The society sponsors annual meetings; meetings devoted to specific clinical or translational aspects of biological approaches to cancer treatment, and is known for being a unique place where clinicians, academicians, and industry leaders meet to define new goals and new approaches that take advantage of recent advances in immunology, cancer biology, and clinical medicine.
Evolution of the iSBTc. The International Society for Biological Therapy of Cancer was founded in 1984 by 40 charter members as the Society for Biological Therapy (SBT), the Society has sought to facilitate the exchange and promotion of scientific information about the use of biological cancer therapies. In its infancy, enthusiasm for SBT continued to grow, as promising scientific breakthroughs in recombinant DNA technology, monoclonal antibody technology and tumor immunology became budding foundations of cancer research. Researchers and scientists believed that new systemic therapeutic treatments would begin to supplant, or at the very least complement, chemotherapy in the fight against cancer. SBT intended to strike a balance of members from academia, government, industry and clinical and basic scientists, all interested in taking the new biotherapies from the bench to the bedside. Scientific and business meetings have been held annually since the first Annual Meeting of SBT in 1986. At the 2002 business meeting, held November 9, 2002, the SBT membership voted to officially change the name of the Society and it thus became the International Society for Biological Therapy of Cancer (iSBTc). The Society currently has over 500 members consisting primarily of MDs, PhDs, RNs, and corporate representatives
History 1986-1991: The founders of the Society believed that SBT would succeed as a vital niche organization with a specialized focus on biological therapies for the treatment of cancer. The American Society for Clinical Oncology (ASCO) was looked at as a model of success for SBT to follow
Benchmarks:
-John K. Whisnant, MD organizes the first SBT Annual Meeting in 1986 in Chapel Hill, North Carolina
-Robert Oldham, MD establishes the Journal of Biological Response Modifiers; this becomes the official Journal of the SBT
-Steven A. Rosenberg, MD, PhD becomes the new editor of the Journal; the official name changes to the Journal of Immunotherapy
-The major biotechnology companies of the era are Schering-Plough and Roche who market interferon alpha, and OrthoBiotech and Amgen who co-market erythropoietin; Amgen also develops and markets granulocyte colony-stimulating factor (G-CSF)
1992 - 1998: Because of the increasing complexity of regulatory compliances and lack of approved therapeutic biological products, the focus of SBT Annual Meetings are often preclinical work and phase I and II trials, as opposed to phase III trials or optimizing the use of approved biologics in anti-cancer therapy. The focus of SBT narrows and the field becomes more challenging for researchers.
Benchmarks:
-Interleukin-2 is granted regulatory approval by FDA for renal cell cancer in May of 1992 and for melanoma in 1998
-In November of 1993, the FDA announces that all biologicals, including patient-specific products that involve modification of the tissue, require an Investigational New Drug (IND) approval; this limits the ability to conduct trials with patient specific products
-Former SBT president, Michael Hawkins, MD and the SBT Board of Directors declare the focus of the Society to be at the translational level of preclinical and phase I trials
-No new therapeutic biological products are approved by the FDA between May of 1992 and November of 1997
-Former president, Richard V. Smalley, MD steps forward to administer the Society as Treasurer from 1994 - 1998 because of increased restrictions and the uncertainty of administrative support from the NCI or industry; he also registers SBT as a not-for-profit corporation in the state of Wisconsin
-SBT member, Antonio J. Grillo-Lopez, MD is the project clinician in the development of Rituxan™; the FDA's approval of rituximab (Rituxan™) in 1997 drives the profitability in the following years for monoclonal antibody treatment which in turn further establishes biological cancer treatments in the field of cancer research
1999 - 2006: Enthusiasm for biological therapy is rekindled as monoclonal antibody treatments come of age and vaccine strategies also begin to strengthen their place in cancer treatments. The Society has a resulting upsurge in membership and meeting participation, thus fostering growth and prosperity as an organization and providing an arena for invaluable information exchange amongst researchers and clinicians. To reflect this growth in both national and international membership, the Society officially becomes the International Society for Biological Therapy of Cancer (iSBTc) and changes its internal structure to a committee-driven Society giving leadership opportunities to many valued members.
Benchmarks:
-Vaccines research begins to flourish with research in autologous tumor cells, autologous tumor cell lines, peptide antigens and the understanding of combinations of antigen sources with dendritic cells
-SBT conducts its first international meeting held in 2000 in Berlin, Germany under the presidency of Michael T. Lotze, MD
-Under the presidency of Robert O. Dillman, MD, SBT officially changes its name to the International Society for Biological Therapy of Cancer (iSBTc) at the Board of Directors meeting in November of 2002
Journals
Journal of Immunotherapy The Journal of Immunotherapy is a peer reviewed, multidisciplinary journal directed to an audience of immunotherapy and biological therapy physicians and researchers and serves as the official journal to the International Society for Biological Therapy of Cancer. The Journal publishes original articles in the form of basic studies, clinical studies, and selected abstracts from scientific meetings and conferences.
See also
Footnotes
- ^ Rotrosen D, Matthews JB, Bluestone JA (2002). The American Cancer Society ( ACS) is the "nationwide community-based voluntary health organization dedicated to "The immune tolerance network: a new paradigm for developing tolerance-inducing therapies". J. Allergy Clin. Immunol. 110 (1): 17-23. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12110811.
- ^ Durham SR, Walker SM, Varga EM, et al (1999). "Long-term clinical efficacy of grass-pollen immunotherapy". N. Engl. J. Med. 341 (7): 468-75. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 10441602.
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