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cancer immune therapy

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    Submitted To: Dr. Abhay Kumar Submitted By: Mudaser Ahmad loneSection : P7905Roll no : A16Registration no: 10907230    Cancer biology C ancer is a class of diseases in which a group of cells display u ncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), andsometimes metastasis (spread to other locations in the body via lymph or blood). C ancer harmsthe body when damaged cells divide uncontrollably to form lumps or masses of tissue calledtumors (except in the case of leukemia where cancer prohibits normal blood function byabnormal cell division in the blood stream). Tumors can grow and interfere with the digestive,nervous, and circulatory systems, and they can release hormones that alter body function.Tumors that stay in one spot and demonstrate limited growth are generally considered to be benigMore dangerous, or malignant, tumors form when two things occur: A cancerous cellmanages to move throughout the body using the blood or lymph systems, destroying healthytissue in a process called invasion. That cell manages to divide and grow, making new bloodvessels to feed itself in a process called angiogenesis. When a tumor successfully spreads toother parts of the body and grows, invading and destroying other healthy tissues, it is said tohave metastasized. This process itself is called metastasis , and the result is a serious conditionthat is very difficult to treat .Physicians and researchers who specialize in the study, diagnosis,treatment, and prevention of cancer are called oncologists. The branch of medicine concernedwith the study, diagnosis, treatment, and prevention of cancer is oncology . C ancers are caused byabnormalities in the genetic material of the transformed cells.These abnormalities may be due to the effects of  carcinogens, such as tobacco smoke, radiation,chemicals, or infectious agents. Other cancer-promoting genetic abnormalities may randomlyoccur through errors in DNA replication , or are inherited, and thus present in all cells from birth. The heritability of cancers is usually affected by complex interactions between carcinogensand the host's genome. Genetic abnormalities found in cancer typically affect two generalclasses of genes. C ancer-promoting oncogenes are typically activated in cancer cells, givingthose cells new properties, such as hyperactive growth and division, protection againstprogrammed cell death , loss of respect for normal tissue boundaries, and the ability to becomeestablished in diverse tissue environments. Tumor suppressor genes are then inactivated incancer cells, resulting in the loss of normal functions in those cells, such as accurate DNAreplication, control over the cell cycle, orientation and adhesion within tissues, and interactionwith protective cells of the immune system. Imm u ne system dysf  u nction HIV is associated with a number of malignancies, including Kaposi's sarcoma, non-Hodgkin'slymphoma, and HPV- associated malignancies such as anal cancer and cervical cancer involves breakdown of immune surveillance as a possibility of cancer  . Excepting the rare transmissionsthat occur with pregnancies and only a marginal few organ donors, cancer is generally not atransmissible disease. The main reason for this is tissue graft rejection caused by MHC    incompatibility . In humans and other vertebrates, the immune system uses MH C antigens todifferentiate between self and non-self cells because these antigens are different from personto person. When non-self antigens are encountered, the immune system reacts against theappropriate cell. Such reactions may protect against tumour cell engraftment by eliminatingimplanted cells. In the United States, approximately 3,500 pregnant women have a malignancyannually, and transplacental transmission of  ac u te le uk  aemia, lymphoma, melanoma andcarcinoma from mother to fetus has been observed . Cancer imm u notherapy Cancer imm u notherapy is the use of the immune system to reject cancer. The main premise isstimulating the patient's immune system to attack the malignant tumor cells that are responsiblefor the disease. This can be either through immunization of the patient (e.g. by administering acancer vaccine, in which case the patient's own immune system is trained to recognize tumor cells as targets to be destroyed, or through the administration of therapeutic antibodies as drugs,in which case the patient's immune system is recruited to destroy tumor cells by the therapeuticantibodies. Since the immune system responds to the environmental factors it encounters on the basis of discrimination between self and non-self, many kinds of tumor cells that arise as a resultof the onset of cancer are more or less tolerated by the patient's own immune system since thetumor cells are essentially the patient's own cells that are growing, dividing and spreadingwithout proper regulatory control. Anti-T u mor Antibodies Can Enhance T u mor Growth Following the discovery that antibodies could be produced to tumor-specific antigens, attemptswere made to protect animals against tumor growth by active immunization with tumor antigensor by passive immunization with antitumor antibodies. Much to the surprise of the researchers,these immunizations did not protect against tumor growth; in many cases, they actually enhancedgrowth of the tumor. The tumor-enhancing ability of immune sera subsequently was studied incell-mediated lympholysis ( C ML) reactions invitro. Serum taken from animals with progressivetumor growth was found to block the C ML reaction, whereas serum taken from animals withregressing tumors had little or no blocking activity. K. E. and I. Hellstrom extended thesefindings by showing that children with progressive neuroblastoma had high levels of some kindof blocking factor in their sera and that children with regressive neuroblastoma did not have suchfactors. Since these first reports, blocking factors have been found to be associated with anumber of human tumors. In some cases, antitumor antibody itself acts as a blocking factor.Presumably the antibody binds to tumor-specific antigens and masks the antigens from cytotoxicT cells. In many cases, the blocking factors are not antibodies alone but rather antibodiescomplexed with tumor antigens. Although these immune complexes have been shown to block the C TL response, the mechanism of this inhibition is not known. The complexes also mayinhibit AD CC by binding to Fc receptors on NK cells or macrophages and blocking their activity    Vaccine Therapy and Antibody Therapy C ancer cells have substances on their outer surfaces that can act as antigens and thus ³mark´ thecells as different or abnormal. Viruses, bacteria, and parasites have cells that are substantiallydifferent from normal human cells because they are truly foreign to the body and are detected bythe immune system. However, the differences between cancer cells and normal human cells may be more difficult for the immune system to detect. Cancer imm u notherapies are designed tohelp the immune system recognize cancer cells and/or to strengthen the immune response to thecancer cells and thus destroy the cancer. The cancer cells¶ antigens may not be different enoughfrom those of normal cells to cause an immune reaction; thus, the immune system may notrecognize the cancer cells as foreign. The immune system may recognize the cancer cells¶antigens, but the immune response may not be strong enough to destroy the cancer. Additionally,some cancer cells themselves may also give off substances that prevent the immune system fromresponding properly. There are two broad classes of immunotherapies, active imm u notherapyand passive imm u notherapy. Active immunotherapies stimulate the body¶s own immunesystem to fight the disease. Passive immunotherapies do not rely on the immune system to attack the disease; instead, they use immune system components (such as antibodies) that are createdoutside of the body to fight the disease. These two approaches are also called vaccine therapyand antibody therapy respectively. In vaccine therapy, or active therapy, the patient is given avaccine that should stimulate the immune system to attack the cancer. In antibody therapy, or  passive therapy, the patient is given antibodies that will hopefully target the cancer but leave thenon-cancerous cells alone. The problem with both approaches is finding substances that theimmune system can target (antigens) which are only present on the cancer cells and not onnormal cells. Sometimes vaccines combined with nonspecific immunotherapy, using additionalsubstances or cells called adj u vants in order to boost the immune system¶s response. Vaccine Therapy Cancer vaccines contain cancer cells, parts of cells, or pure antigens that increase the immuneresponse against cancer cells that are already present in the body. They are considered activeimmunotherapies since they are meant to trigger your own immune system to respond. They areconsidered specific because they do not result in a generalized immune system response. Theycause the immune system to produce antibodies to one or several specific antigens, and/or to produce Killer T cells to attack cancer cells that have specific antigens. There are severaldifferent types of vaccines; among them are tumor cell vaccines, dendritic cell vaccines,antigen vaccines, anti-idiotype vaccines, and DNA vaccines. Tumor cell vaccines use cancer cells that are removed from the patient during surgery. The tumor cells are then killed so theycannot form more tumors. The tumor cells may be modified with chemicals or genes, or mixedwith other substances known to increase the immune response in an attempt to improve theeffectiveness of the vaccine. The tumor cells are the injected back into the patient. The antigens
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