HEMATOLOGY AND ONCOLOGY
Canceris associated with global immune suppression of the host. The humanimmune system fights the pathogens and harmful antigens that mayinvade the body. However, this is not always the case as there areautoimmune diseases which turn the body against itself. Cytotoxic TLymphocytes antigen-4 is the antigen that is responsible for alteringthe body’s immune system by changing the T-cells signals. Thestudy, therefore, aims to find the role of CTLA treatment and how itcan be influenced by the science of hematology and oncology. Thestudy is also concerned with the role of CTLA treatment ineradicating autoimmune diseases. Finally, the study seeks to find outthe role of CTLA treatment on graft survival.
Hematologyis defined as a branch of medicine which is usually associated withthe study of blood, the blood-forming organs, and blood diseases.Specialists who have studied hematology deal with the diagnosis,treatment and management of patients with blood disorders andillnesses (Wieger J. & Norde, 2012). Oncology, on the other hand,is a branch of medicine that deals with the prevention, diagnosis andtreatment of cancer. In the battle against cancer, there are threecritical components. Prevention, early diagnosis and treatment.Oncology incorporates these three elements to ensure that they candetect and be one step ahead in this fight. Cancer is associated withthe immune suppression of the host. CTLA-4(cytotoxicT-lymphocyte-associated protein 4) also known as CD152 (cluster ofdifferentiation 152), is a protein receptor that functioning as animmune checkpoint, ward off the immune system. CTLA-4 ensure that theT cells are not able to recognize and eliminate foreign antigens andthus, most often tumour cells can evade immune recognition anddestruction (Oudard, 2013). The study will focus on the role ofhematology and oncology in CTLA treatment, the role of CTLA treatmentin graft survival and its role in autoimmune diseases.
Goalsof the study
Thereare several goals of this study. First is to understand howhematology and oncology can be used to combat the effect of CTLA-4.Second, to illustrate the role of CTLA treatment on auto-immunediseases. Third, to understand the role of CTLA treatment on graftsurvival.
Themethod used to carry out this study was the collection of data fromsecondary sources. These includes web sites, books, and journalarticles. The data obtained was then precisely compiled to come upwith this presentation.
Roleof hematology and oncology in CTLA treatment
Formany years, most medicine graduates have mainly focused on one of thedisciplines of medicine, either hematology or oncology. According toDr Drew, this is however set to change. Most of the specialists inthe field of cancer have found the need to train in both disciplines.Thus, the rise of hematology-oncology programs. Specialists now canfocus not only on oncology issues but also cover areas of hematologyand improve on their knowledge (Reed, 2005). Hematology is the studyof blood while oncology is the prevention, diagnosis and treatment ofcancer. The two disciplines when they work hand in hand, it will bepossible to combat the effects of cancer.
CTLA-4is uttered on the surface of T cells and transmits an inhibitorysignal to T cells. The mechanism under which CTLA-4 acts in T cellsis still subject to controversy. Biochemical evidence suggests CTLA-4recruited a phosphatase to T-cell receptors, thus attenuating thesignal. CTLA-4 may function via modulation of cell motility orsignalling through PI3 kinase (Margaret K. & Callahan, 2011).
Cancerimmunotherapy is the application of the immune system to treatcancer. Immunotherapy exploits the fact that cancer cells havedifferent molecules on their surface that can be detected by theimmune system. Cancer immunotherapy arose from clinical advances inoncology and immunology. Ipilimumab (MDX-010 and MDX-101), is amonoclonal antibody that works to activate the immune system bytargeting CTLA-4. Cytotoxic T lymphocytes (CTLs) can spot and killcancer cells. Ipilimumab turns of the inhibitory mechanism thathinders the function of CTLs. Ipilimumab was ratified by the U.S. FDAin 2011 for the treatment of melanoma, a type of skin cancer.Ipilimumab is among the few monoclonal antibodies that are approvedby the FDA for cancer treatment. Other monoclonal antibodies includeNivolumab, Ofatumumab, Pembrolizumab, and Rituximab (Couzin, 2013).
Roleof CTLA treatment in autoimmune diseases
Anautoimmune ailment develops when your immune system decides yourhealth cells are foreign. This occurrence results in the immunesystem attacking healthy cells in the body. Autoimmune diseases,depending on the type can affect one or numerous body tissues. It mayalso result in abnormal organ growth and changes in organ function.There are more than 80 forms of autoimmune ailments. Currently,treatment for autoimmune disease focuses on relieving symptoms sincethere is no cure. Some of the most frequent autoimmune diseasesinclude rheumatoid arthritis, systematic lupus erythematosus, celiacsprue disease, pernicious anaemia, vitiligo, and scleroderma. Othersinclude psoriasis, inflammatory bowel diseases, Hashimoto’sdisease, Graves’ disease, Addison’s disease, reactive arthritis,Sjogren’s syndrome, type 1 diabetes (Margaret K. & Callahan,2011).
Thecause of autoimmune disease is unknown. Although, many theories tryto estimate the cause or triggers of the immune system to attack thehealthy cells. They include bacteria or virus, drugs, chemicalirritants, environmental irritants. It is also believed that it ishereditary and such chances of inheriting the disease are high. Someof the most frequent symptoms are fatigue, fever, and general malaise(Yi-chi M. Kong, 2014). However, the symptoms vary since there arevery many different types of autoimmune diseases. The most commonlyaffected organs are joints, muscles, skin, red blood cells, bloodvessels, connective tissue, and endocrine glands (Pardoll, 2012).
Theimmune system has established several mechanisms to prevent harmfulactivation of immune cells. Autoimmune diseases occur due to thefailure of the immune system to control non-responsiveness ortolerance to self-antigens. Studies suggest that coinhibitorymolecules are key in the prevention of autoimmune diseases because adefect or mutation in these molecules promotes autoimmunity andpolymorphisms of these genes. CTLA-4 has been suggested to beassociated with various autoimmune diseases including Graves’disease, autoimmune hypothyroidism, type 1 diabetes, systemic lupuserythematosus (SLE), and celiac disease. These findings suggestCTLA-4 is critical in the prevention of autoimmunity in multipleorgans through various mechanisms (Nakajima, 2012).
Itis anticipated that blockade of B7-CD28 interactions mightpreferentially hinder lymphocytes that are in the course ofcountering to self-antigens without affecting resting T-cells thatrecognize other antigens. To accomplish this, scientists figured outthat CTLA-4 binds B7-1 and B7-2 with much affinity than CD28 does. Asynthesis protein of extracellular domain of CTLA-4 and the constantregion of IgG blocks the interaction between B7 molecules and CD28,therefore, inhibits T-cell activation. Abatacept is one of theclinical applications of the CTLA-4 Ig. This type of implementationis a fusion protein composed of the Fc fragment of a human IgG1. Ithas shown tremendous results in rheumatoid arthritis (RA) patients.The use of Abatacept treatment results in improvements in the signsand symptoms of RA, which includes inhibition of structural damage.Belatacept (LEA29Y) is also a CTLA-4 Ig. It is different fromAbatacept by substitution of two amino acids, which converse astronger binding avidity for B7 and a greater inhibition of T-cellactivation. Phases 1 and two clinical trials of multiple-dose ofBelatacept has revealed efficiency in the treatment of RA (Nakajima,2012).
Roleof CTLA treatment in graft survival
Graftsurvival refers to the success of the kidney transplant. The expectedrate is defined as the rate that would be expected for the patientsserved by this centre, given the characteristic mix of the recipientand donor and the experience of similar patients.
Toleranceremains the ideal for permanent engraftment of transplanted organs.CTLA-4 has the following roles: It hinders the development oftolerance to the soluble antigen, it augments antitumour responsesand enhances the chances of autoimmune diseases. CTLA-4 signalling isvery crucial for the induction of long-term allograft survivalthrough CD28 blockade with CTLA-4 immunoglobulin (CTLA-4 Ig).Blocking of CD28 dependent T-cell activation has been used inexperimental models of transplant rejection and autoimmunity ofdiseases to regulate the immune responses of the body. In most cases,treatment with CTLA-4 Ig resulted in prolonged graft survival,donor-specific tolerance, and reduced the lethality of graft vs. hostdiseases. CD45 is a potent immunomodulatory target. Use ofanti-CD45RB can enhance long-term engraftment and donor-specifictolerance to the allograft. (Scott, 2001).
Effortshave been made in the medical field to target the CD28 and CTLA-4signalling pathways, to enhance anti-tumour immunity,. Most tumoursare weakly immunogenic. This is because the tumours lack thecostimulatory molecules needed to activate T cells.7 Tumour cellsthat express the B7 molecules on their surface usually induce thestrong responses against the transfected tumour cells and originalparent cells. A proper understanding of these pathways CD28 andCTLA-4, combined with therapeutic approaches will have major clinicalapplications in the breakthrough of graft survival (Steven, 2015).
Itis evident much research has been done to come up with ways to winthe fight against cancer. CTLA treatment has significant results asclearly illustrated in the study. Studies have demonstrated thatblockade of CD28 can be used to modulate the immune responses of thebody. This will help ensure that patients have a high chance ofprolonged graft survival and minimal chances of graft-host relatedcomplications. CTLA-4 Ig treatment is a major breakthrough in themedical study of hematology and oncology. CTLA-4 Ig preventsautoantibody production, enhances prolonged graft survival, andensures donor-specific tolerance. It is my hope that future clinicaltrials will find more findings on CTLA treatment and assist create asolution to the menace that is brought about by cancer and autoimmunediseases. Medical breakthroughs in the field of hematology andoncology will also encourage more medical graduates and graduands topursue the related medical programs in the area in a bid to be moreconversant with the new findings in the studies. It will also enhancethe livelihood of people who had undergone organ transplant byensuring they have a higher chance of graft survival.
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