Traditional Monoclonal Antibodies and Recombinant Antibodies
Introduction: Antibody is a special molecule that present in our bodies to fight against infections and stimulate immune response. Typical antibody is a “Y” shaped molecule consists of two H (heavy) and two (light) chains. Two antigen-binding fragments (Fabs) are linked with a constant region (Fc)(Brekke and Sandlie 2003). After the discovery of murine monoclonal antibodies produced by hybridoma cells developed by Kohlor and Milstein(Kohler and Milstein 1975), the role of monoclonal antibodies in therapeutics and clinical diagnostics are increasingly important in the last three decades (Laffly and Sodoyer 2005). The term monoclonal antibody is defined as an antibody molecule which is monospecific and derived from a single B cell clone. Results in using fully murine monoclonal antibodies in therapeutics are not ideal and problems aroused in triggering unwanted human immune responses. These problems force the generation of recombinant antibodies in the replacement of traditional monoclonal antibodies. Tailor-made recombinant antibodies fragments increase flexibility both in immunotherapy and immunodiagnostics. The application of minimal form of functional antibodies single-chain antibodies (scFvs) are the most popular form of recombinant antibodies fragments as diagnostic agents (Hagemeyer et al. 2009). In this assignment, the comparison between traditional monoclonal antibodies and recombinant antibodies as therapeutics agents and diagnostics tools will be discussed. From the example of tragedy TGN 1412, the potential risk of using recombinant antibodies in therapeutic agents should not be ignored. Finally, future perspective of recombinant antibodies in gene therapy and using polyclonal antibodies as novel immunotherapeutic strategy will be discussed. Theoretically, probably any kind of monoclonal antibodies can be produced with the aid of hybridoma technique. The continuous culture of hybridoma cells creates an inexhaustible supply of monoclonal antibodies in the laboratories by cell culture or rodent(Nelson, Reynolds et al. 2000). Its highly specificity, stability and homogeneity are ideal for diagnostics and in therapeutic purposes. After the introduction of the first FDA approved drugs OKT3 launched into the market in 1986, the results of using fully murine monoclonal antibodies in human was not promising (Chatenoud, Baudrihaye et al. 1986; Chatenoud, Jonker et al. 1986). This is because murine originated monoclonal antibodies triggered several immunogenic responses in human body. One of the problems arise is human anti-mouse antibodies (HAMA) or anti-globulin antibodies (HAGA) response (DeNardo, Bradt et al. 2003; Presta 2006) generated against the administrated murine antibodies. Studies showed that around 30-75% of patients with solid tumors and relapsed B-cell malignancies developed HAMA response after exposure to murine antibodies (Smith, Nelson et al. 2004; Majidi, Barar et al. 2009). The activation of HAMA response is mainly due to the host antibodies generated against the idiotopes of the administered murine antibodies. Moreover, rapid clearance of murine Abs shortens its serum half-life and relatively ineffective to trigger cytotoxic effect (e.g. ADCC and CDC) compared to human antibodies hindered murine Abs as therapeutics agents (Presta 2006). Based on the above unresolved problems, with the aid of genetic engineering, murine monoclonal antibodies are modified to become less immunogenic and enhance potency in therapeutics and diagnostics. Three different types of recombinant antibodies are generated: chimeric, humanized and human antibody. In chimerization, the murine variable region is fused with the human constant region forming chimeric antibodies(Presta 2006). This modification imitates the human immune system. Although chimeric antibodies is less immunogenic but may trigger human anti-chimeric antibody responses (HACA)(Baert, Noman et al. 2003). Further maturation technique is humanization (hyperchimeric). In this technique, only the complementarity determining regions (CDRs) from the murine antibody was grafted into a human constant and variable regions (Smith, Nelson et al. 2004). By resurfacing, reshaping and hyperchimerisation of hyperchimeric antibody, the antibody binding affinity improved. Although the above methods minimize immunogenicity, but immune response result of xenografting may occur. Finally, human antibodies can be generated by transgenic mice and in vitro combinatorial libraries (Brekke and Loset 2003; Brekke and Sandlie 2003; Presta 2006). Antibodies which generated under this method are expected to be identical to human antibodies with clinical significant without any side effects. One of the examples in combinatorial library approach for the selection of antibodies is by phage display technology in which antibody variables domain are expressed as fusion protein as coated on the surface of the bacteriophages. Under combinatorial library approaches and transgenic mice, the chance of getting fully human antibodies are higher when compared to hybridoma and chimeric antibody technologies. In addition, single-chain variable fragment (scFv) and Fab fragment can be isolated (Brekke and Loset 2003; Brekke and Sandlie 2003). Therapeutics application Fc portion in an intact antibody trigger effector function which is undesirable for therapeutic applications. Therefore, for a desirable antibodies design for cytokine inactivation or receptor blockage, the main considerations of antibody design are: size, tissue penetration, distribution, half-life, effector function, affinity, stability and immunogenicity. scFv and Fab fragments are preferred as choice of preference when compared to traditional antibodies because of smallest in size, high binding affinity, specificity, good tissue penetration and reducing immunogenicity due to HAMA response. scFv and Fab antibodies have a shorter half-life than whole antibodies and this drawback can be overcome by PEGylation. In addition, the attachment of PEGylation of murine monoclonal antibody reduces HAMA response of the host after administration(Laffly and Sodoyer 2005). Applications of monoclonal antibodies are vastly employed in therapeutic agents (e.g. treatment of cancer) and in clinical diagnostic (e.g. histopathological diagnosis). Humanized mAbs (transgenic mice) (resurfacing, reshaping and hyperchimerisation, etc) Phage display technology (Fabs and Fvs) In recent years MAbs have become very important commercial reagents, and currently contribute to over 30% of biopharmaceuticals in development and production. To date, 10 different MAbs have achieved FDA approval, with others in phase III trials.4 Applications Antibody conjugates (Majidi, Barar et al. 2009) Unconjugated mAbs (Majidi, Barar et al. 2009) rAbs for cancer therapy immunohistology genetic immunotherapy(Pelegrin, Gros et al. 2004) scFv for diagnostics tools (size, immunosensor, inhibition of imnflammation and complement system) (Hagemeyer, von Zur Muhlen et al. 2009) Problems polyclonal vs monoclonal therapeutics (Haurum 2006) TGN1412 incident (Self and Thompson 2006) References: Baert, F., M. Noman, et al. (2003). “Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease.” N Engl J Med 348(7): 601-608. Brekke, O. H. and G. A. Loset (2003). “New technologies in therapeutic antibody development.” Curr Opin Pharmacol 3(5): 544-550. Brekke, O. H. and I. Sandlie (2003). “Therapeutic antibodies for human diseases at the dawn of the twenty-first century.” Nat Rev Drug Discov 2(1): 52-62. Chatenoud, L., M. F. Baudrihaye, et al. (1986). “Restriction of the human in vivo immune response against the mouse monoclonal antibody OKT3.” J Immunol 137(3): 830-838. Chatenoud, L., M. Jonker, et al. (1986). “The human immune response to the OKT3 monoclonal antibody is oligoclonal.” Science 232(4756): 1406-1408. DeNardo, G. L., B. M. Bradt, et al. (2003). “Human antiglobulin response to foreign antibodies: therapeutic benefit?” Cancer Immunol Immunother 52(5): 309-316. Hagemeyer, C. E., C. von Zur Muhlen, et al. (2009). “Single-chain antibodies as diagnostic tools and therapeutic agents.” Thromb Haemost 101(6): 1012-1019. Haurum, J. S. (2006). “Recombinant polyclonal antibodies: the next generation of antibody therapeutics?” Drug Discov Today 11(13-14): 655-660. Kohler, G. and C. Milstein (1975). “Continuous cultures of fused cells secreting antibody of predefined specificity.” Nature 256(5517): 495-497. Laffly, E. and R. Sodoyer (2005). “Monoclonal and recombinant antibodies, 30 years after.” Hum Antibodies 14(1-2): 33-55. Majidi, J., J. Barar, et al. (2009). “Target therapy of cancer: implementation of monoclonal antibodies and nanobodies.” Hum Antibodies 18(3): 81-100. Nelson, P. N., G. M. Reynolds, et al. (2000). “Monoclonal antibodies.” Mol Pathol 53(3): 111-117. Pelegrin, M., L. Gros, et al. (2004). “Monoclonal antibody-based genetic immunotherapy.” Curr Gene Ther 4(3): 347-356. Presta, L. G. (2006). “Engineering of therapeutic antibodies to minimize immunogenicity and optimize function.” Adv Drug Deliv Rev 58(5-6): 640-656. Self, C. H. and S. Thompson (2006). “How specific are therapeutic monoclonal antibodies?” Lancet 367(9516): 1038-1039. Smith, K. A., P. N. Nelson, et al. (2004). “Demystified…recombinant antibodies.” J Clin Pathol 57(9): 912-917.
San Jose State University Social Work Practice Education Home Visit Discussion
help writing San Jose State University Social Work Practice Education Home Visit Discussion.
Observe two or more people interacting in a professional setting. Given COVID restrictions ensure you’re following distancing and all safety measures. If you are able to make observations in a social work agency, whether your workplace, or your placement internship, you may do so; however, please ensure that your observations are free of any identifiers (names/recognizable characteristics). If you don’t have access to observable interactions please use the video provided of a home visit with Dory and David: Write a three page (excluding cover page), double spaced paper describing in detail:1. People’s behaviors, conversations, body language, expressions. You should document only what you see or hear or smell.2. If you become aware of any assumptions or biases on your part while writing your observations, please document those in a final paragraph. Please be mindful of grammar, punctuation, and overall presentation. Use APA7, save as PDF As you record your initial observations it may be helpful to note characteristics of: Actors, Space, Objects, Acts, Activities, Events, Time, Mood, Goals/Objectives.
San Jose State University Social Work Practice Education Home Visit Discussion
A Review of Farley Mowat’s ‘Lost In The Barrens’
Lost In The Barrens by Farley Mowat is a fictional wilderness survival novel which introduces two young teenagers, Jamie Macnair and Awasin Meewasin. At the beginning, Jamie goes up to the northern part of Canada to live with his uncle, Angus Macnair. As Jamie arrived, he quickly introduced to Awasin and becomes friends with him. He finds out that Awasin is the son of the Cree’s chief. The leader of Chipewyan (the Cree’s rival), Denikazi along with his men come for help as they were starving due to lack of deer in the north.. Awasin’s mother had suspicion that the Chipewyan were trying to deceive them, although the boys still agree to go to the Indian village to prove that they need supplies. Both Jamie and Awasin join the Chipewyan on their way back to the camp of the Chipewyan and as they arrive, Denikazi thought that the boys were going to join them in the hunt but told both the boys to return to the camp with two young Chipewyans. Denkazi warned them that… If they were to encounter Eskimos, they were to abandon the camp and go home. In this novel, both the Chipewyans and the Crees are afraid of the Eskimos. (Denikazi told the both the boys an incident where the Chipewyans went on a hunt for deer in the north and encountered Eskimos. The Eskimos got guns and fought the Chipewyans which led to the fear of the Eskimos). Jamie, Awasin and the two Chipewyan boys go back to the camp but as soon as they get back… Jamie decides to go explore and tricks Awasin to join him. They venture up with their boat to the stone house that one of the two Chipewyans boys had told them about. They try to find it but they hit a whirlpool and they barely survive it. Gathering what they could from their broken canoe, they realize they don’t have enough to survive, they cannot use their canoe and now they are stranded in the barrens. The two young Chipewyan boys notice that both Jamie and Awasin have disappeared, so they go searching for them. The two boys saw an Eskimo kayak and ran back to the camp. Jamie and Awasin decide to go all the way to where Denikazi and the other hunters, so they can join them. But one of Denikazi’s men see an Eskimo and the whole group flees, passing through Jamie and Awasin’s camp during the night. Later on, Jamie and Awasin soon realize that Denikazi and his men have passed by their camp already and decide that they have to get some sort of shelter and food for their survival. They soon find the stone house and figure out that it was a grave of a Viking. Soon, they go hunting for does, ground squirrels, fish and buck(that migrate). Winter arrives and they survive it by discovering a valley where there is wood for them to build shelter and create heat. There were also bucks that were not migrating and spending their winter here. One day, the weather is not as cold as any other winter and the boys decide to head back home gathering up most of their supplies onto a sled they have created. They find two dogs and the sled pulled by the two dogs they recently found. Their names were Fang and Ayuskeemos and they were huskies belonging to the Eskimos. Trouble occurs with the two boys when they get snow blindness and eventually the boys realize that they can’t make it and try to go back to their cabin. On their way back, a blizzard storm comes and they find a igloo where they crawl in. In the morning, they realize that the igloo belonged to an Eskimo as he returned. The Eskimo’s dog get into a fight with Fang and Ayuskeemo and it is broken up by Jamie and the Eskimo. Working together, Jamie and Awasin learn that the Eskimo’s name is Peetuk, the son of a white Englishman and an Eskimo woman. They become friends and visit the Eskimo’s where the three finally make it back to the Cree camp. Jamie and Awasin finally make it back home where they established their whole adventure was all about friendship, trust and survival. Author’s Biography War Service Farley Mowat was part of the military during the Second World War and was commissioned as a second lieutenant into the Second Battalion. He went overseas joining the Canadian Army in the United Kingdom. He served throughout the war as a commander and moved to Italy in September of 1943. He stayed in Italy in the first Canadian infantry division for most of the way, eventually promoted to captain. Later on, Mowat was discharged at the conclusion of the Second World War in 1945 as a captain. Lost of the Barrens can be reflected towards the Second World War Mowat was in. In comparison, being in war and being lost in the barrens reflect on survival. Mowat uses his writing in this case to talk about survival. Lost in the Barrens is all about survival and he puts his writing to reflect what he has gone through in the past… Except as a teenager in the wilderness. Early Life Farley Mowat was born in Belleville, Ontario on May 12th 1921 and he has been a writer since he was a child. He recalls composing “mostly verse†living with his family in Windsor from 1930 to 1933. He published a regular column based on observation of birds in the star Phoenix after moving to Saskatoon with his family. It seems as Fowat’s life is reflected on his writing, comparing his imagination. Lost of the Barrens is full of imagination which Jamie shows throughout the whole book. Jamie is the character that has the biggest imagination in the whole novel. He tries imagine himself in the wilderness and his curiosity kills him to the point he tricks Awasin to join him to explore what he imagines. In comparison, Mowat is similar in a way. As a child, Mowat had a huge imagination where he reflects his creative writing and his imagination into a story. He’s reflecting the imagination Jamie has with the imagination he has in his writing for Lost in the Barrens. Historical Time Period (Era) The Cold War The Cold War was a political conflict that existed after World War II between the communism due to the Soviet Union and the powers of the Western World, primarily the United States and its allies. Although the Soviet Union and the United States did not attack directly, they expressed their conflicts indirectly through military alliances, strategic conventional force drops, proxy wars, propaganda and nuclear arm races. The Cold War featured periods of the relative calm and of international high tension (specially) the Korean war and the Vietnam war. This time era relates to Lost in the Barrens shows the rivalry between the Chipewyan and the Crees as they were always enemies in the book as there would be always competition for food and land. It can be a comparison with Korean War that happened between both South Korea and North Korea. The Korean war happened due to communism and democracy for the dominance for each section of Korea. Mowat reflects the conflict between the Cree and the Chipewyan to the conflict that North Korea and South Korea had. Art in the 1950s Early 1950s Jackson Pollock and Willem De Kooning were enormously influential to the art industry. Although, during the late 1950s, Barnett Newman and Mark Rothko’s painting became more in focus to the next generation. Pop Art use the iconography of television, photography, comics, cinema and advertising. With its roots in dadaism, it started to take form towards the end of 1950s when some of European artists started to make the symbols and product of the world of advertising and propaganda the main subject of their artistic work. Art is reflected in Mowat’s writing comparing Jamie’s handcrafting skills to the 1950s. Mowat wanted to reflect how art was a part of the time era he was in while writing this novel, making Jamie the artistic one… being able to craft shelter for their safety. Genres Fiction A fiction is a type of genre where the narrator deals with events which is imaginary. There are different types of fictions, but Lost in the Barrens was written as a semi fictional novel. It is set with two teenagers whom do realistic things (surviving in the wilderness with what they have). The two, Jamie and Awasin go join a tribe to hunt but then get lost and stranded in the barrens… Although on the contrasting side… where if two teenagers were to be lost in the barren land wilderness; they would most likely not survive. Here, this is reflected on Mowat’s past with his experience with his imagination. Fiction narration is usually creative writing that is made up by the author using their imagination. Mowat uses his writing to express his imagination in comparison to a fictional novel with is usually written using one’s imagination. Wilderness Survival Wilderness survival is a type of genre where the narrator deals with events in the wilderness. Lost in the Barrens sets a good example of wilderness survival. The two teenagers, Jamie and Awasin get lost in the barrens, where they must strive to survive. Awasin knows the wilderness well, so he is able to hunt for food. Jamie knows how to craft object, which leads to Jamie being the person making all the shelters. Mowat’s writing is reflected in the novel to a combination of his experience in the war and the experience he had in the north of Canada with the Inuits. In comparison to Jamie and Awasin, he reflects his experience in the World War II with the imagination of what he saw in the north of Canada to write this novel. Themes Man vs. Nature Man vs. Nature is a element that is a part of fictional literature. It is usually defined as a problem and nature is usually either the protagonist or antagonist. In Lost in the Barrens, nature is known as the true antagonist. Both the boys, Jamie and Awasin struggle to survive in the harsh conditions they are in. They show their true courage by hunting and surviving a grizzly bear attack. Both the boys have different variety of skills; Awasin being able to hunt, fish and make clothing. Awasin is proven to be clever by igniting a fire with what he is given. Jamie, in the other hand is the creative one. He is the one who builds the shelter (stone igloo and wooden cabin). He is able to think outside the box and with both their traits, they are successful with beating nature with their teamwork. Man vs. Nature is apart of fictional literature which is where Mowat’s creative writing comes in. Mowat uses his imagination and past experience to reflect how he feels towards a certain situation. He has also been in wars which is where he reflects his war experience with a part of this novel. Being able to survive a war is similar to surviving the wilderness with no supplies. Intercultural Friendships Intercultural friendships is a theme where people of different cultures and backgrounds work together and gain trust from one another. In Lost in the Barrens, Awasin and Jamie became friends when they first met but became a lot more closer when they relied on each other to survive. Near the end of the novel, when the boys were barely going to survive… Peetyuk, an Eskimo came and rescued them. Eskimos were known as a dangerous group towards the Cree and the Chipewyan. Jamie helps Awasin trust Peetyuk although the Crees have always been suspicious and afraid of the Eskimos. Mowat’s writing is reflected in the novel with his past. With the past experience he had with the Inuits up on the north. He was outraged at the Inuits where they were racist towards his skin colour. His experience is showing that trust must be put within all races for a world of freedom and acceptance. Conclusion Personal, I really enjoyed this novel for what it was. I never expected it to be enjoyable, the novel cover and description made the novel look extremely dull and boring. I’m extremely surprised that an brown coloured person and a white coloured got along in the novel, which caught me extremely off guard. The novel had a lot of adventure, action, scenes where you could just imagine in your head and just pretended you were just there and lots of intensity. There is a lot of teamwork… Awasin being the knowledgeable one with the wilderness and Jamie having the gift of being able to craft objects, making shelter later on. Farley Mowat is an excellent author who has a lot of imagination and creativity with his writing. He relates a lot of his observations to his writing and adds in his imagination towards his novel(s). I would recommend anyone who has a huge imagination and enjoys nature and camping to read this novel. It may look extremely boring and dull, but later on… It gets REALLY (see how I emphasize on really) interesting and enjoyable. I can understand why this novel won two awards. Biblography “1950s – Wikipedia, the free encyclopedia.” Wikipedia, the free encyclopedia. N.p., n.d. Web. 1 Jan. 2011. . “Cold War International History Project’s Cold War Files.” Woodrow Wilson International Center for Scholars. N.p., n.d. Web. 1 Jan. 2011. . “Farley Mowat.” Eco Books. N.p., n.d. Web. 1 Jan. 2011. . “Mowat, Farley – The Canadian Encyclopedia.” The Canadian Encyclopedia. N.p., n.d. Web. 1 Jan. 2011. . Mowat, Farley. Lost in the Barrens; . [1st ed. Boston: Little, Brown, 1956. Print.]
Write a 5-6 page report on Screening and Selecting Internal Candidates
Write a 5-6 page report on Screening and Selecting Internal Candidates.
OVERVIEW: Write a 5–6 page report describing the process you used to select the best three candidates for CapraTek’s regional sales representative positions. RESOURCES: Arthur, D. (2012). Recruiting, interviewing, selecting, and orienting new employees (5th ed.). New York, NY: AMACOM.chapter 15. Heneman, H. G., III, Judge, T. A., & Kammeyer-Mueller, J. (2015). Staffing organizations (8th ed.). Boston, MA: McGraw-Hill Education. Chapters 6 and 10–12. INSTRUCTIONS: You have written a job description for CapraTek’s regional sales representative positions and determined job requirements. Now it is time to determine testing methods and choose the top three candidates to interview. Requirements After reviewing the CapraTek regional sales representative job description and requirements you developed for Assessment 5, use the Candidate Selection media piece to review the candidates’ resumes. In a 5–6 page report, include the following in your explanation of the candidate selection process: Explain why and when candidate background checks will be authorized. Identify pre-employment screening tests for the position being recruited.Articulate possible legal issues associated with candidate screenings.Select assessment methods to use based on the job being recruited and the budget available.Develop the sequence in which methods will be used to screen applicants.Explain how technology will impact choice of screening and selection methods.Design a final candidate selection process for the position being recruited.Describe the method you would use to make your final hiring decision (compensatory, hurdles, weighted, et cetera).Determine which candidates meet the basic job requirements.Identify the top three candidates to interview for the position.Explain your rationale for why the selected candidates should be interviewed. Additional Requirements Times New Roman font, 12 point.Double-spaced, typed pages.
Write a 5-6 page report on Screening and Selecting Internal Candidates