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Tuesday June 19, 2001

  1. 1. Holder 1 The Groundbreaking Career as a Research Associate in Cancer Immunology Report • Ashley Holder • Grade 12 • • Ms. Mary Glodowski • Juanita High School • • February 28, 2003 • • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  2. 2. Holder 2 Table of Contents Report Report Page 3 Bibliography Page 13 Journal Notes Page 16 Interview Page 18 Impressions Page 19 • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  3. 3. Holder 3 Research Associate in Cancer Immunology A research associate is generally in charge of research and development on projects, usually with others. He observes, analyzes, and interprets results. Basically a research associate is knowledgeable in his area of study and can do anything involving research that includes analyzing data and results, preparing technical reports, participating in scientific conferences, or even conducting experiments. According to Jeff Johnson, Senior Research Associate at Corixa Corporation, Research Associates are the foundation for the development of immunological and other drug developments. They provide their supervisors with the results from their own experiments. Their reports and interpretations become the information that their supervisors use to determine where to go next in the drug’s development. To be a research associate in cancer immunology, one must have a college degree in biological science, chemistry, immunology, or molecular biology. It is helpful to have computer skills. Also, one must have experience with radioisotopes, tissue culture, column chromatography, protein determinations, immunoassay, and western blobs. Job responsibilities actually vary from company to company, but generally include the preparation and isolation of tumor antigens from specimens. One must also perform biological analysis and immunological assays in order to monitor antigens. He or she may also research and develop immunological assays using reagents. Other responsibilities might include the recording and logging of lab equipment as required for the Cancer Laboratory Practices (GLP). While on the surface, a typical workday lasts from 9 AM to 5 PM, a typical research associate can spend untold hours in the lab. One would not blink twice to hear that an associate stayed hours after “closing” to finish an experiment or to complete a • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  4. 4. Holder 4 report. At least half of Jeff Johnson’s workday is data entry and computer analysis. He also spends a lot of time preparing and carrying out experiments and then going to meetings to present his findings. A research associate can become a senior research associate when he or she has experience for a number of years as a member of a clinical team conducting studies (Phase I-Phase IV) according to federal regulations and ICH guidelines. He or she, as a senior research assistant, is responsible for either writing of supervising someone writing the clinical reports or documents for publication. In most instances, to become a Supervisor, one must have a Ph.D. However, new policies at Corixa allow research associates to become supervisors, even if they do not have a Ph.D. They must go through an extensive application and interview process. Salaries for a research associate range from about 20 dollars an hour to nearly 50 dollars an hour. The huge discrepancy in wage is based mainly on experience and education level. Also, company and area of the country play roles in salary determination. Mentorship with a Research Associate Getting into the Corixa Corporation building was a challenge; security was taken seriously. The “Average Joe” could not walk into the building without first calling the security guard. Once inside, I had to check in with the receptionist on the second floor, getting a visitor pass in order to continue into Corixa. About five minutes later, Jeff Johnson came down to show me the way to his lab/work station. It was located in a huge room with 20 other research associates. Each had his or her own glorified cubicle style • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  5. 5. Holder 5 station. The general atmosphere was relaxed. Each scientist was working on his or her own project, mumbling to his or her self about one thing or another. Jeff Johnson, as I learned, had been a Corixa for just over 5 years. He attended Seattle Pacific University and earned a Bachelors of Science in Biology and Environmental Studies with a Chemistry Minor. Just out of college, he first did research at Fred Hutchinson Cancer Research Center from 1993-1997. There he was able to acquire the invaluable skills needed as a research associate. Although his experience at Fred Hutchinson Cancer Research Center was precious, he decided to work at Corixa Corporation in 1997. According to Jeff Johnson, many people right out of college do research at the Fred Hutchinson Cancer Research Center to gain the experience needed to get a job at a private company. Fred Hutch is government run. This brought many obstacles into his research; the first of which being finances. Supplies at the Fred Hutchinson Cancer Research Center were budgeted. All supplies were bought as cheaply as possible. Also, salary was significantly less at The Hutch. Now at Corixa, Jeff Johnson no longer has to pay as close attention to the price of supplies. Except for expensive machinery, he can order what he needs without worrying about money. Taking a tour of Corixa was interesting. I was shown different floors, each floor specializing in its own area of cancer treatment development. For instance, on the upper floor, research associates and other scientists were working on the purification of certain samples to be run in experiments. I was then shown where all the samples are kept and where the CHO was being produced and stored. I found it funny to look at lab areas and see all of the open container violations that I would be marked down for during labs. When I asked Mr. Johnson about it he laughed and said that he should be keeping everything more clean, but when you’re in the real world of science, such small • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  6. 6. Holder 6 violations are not as important. He made it clear however, that certain experiments required sterile environments in which he follows impeccable lab procedure. Jeff Johnson was extremely knowledgeable. The majority of time at Corixa (about two hours), was spent listening to him explain how certain equipment was used and then his explanation of how antibodies were used to treat cancer. He even talked about certain genes and DNA that Mrs. Glowdowski had taught the class weeks earlier. Because of Biotechnology Class and earlier research, I was able to understand the majority of Mr. Johnson’s technical jargon. Later in the afternoon, I was given the opportunity to see the results of one of Jeff Johnson’s experiments completed the previous day. This particular experiment had to do with narrowing down a certain characteristic found in a certain kind of cancer, but for confidentiality reasons and my comprehension level, he was not able to go into much more detail. He did, however, explain to me how to read the chart in which the results were reflected. The graph looked like two mountains, one representing a control, the other representing the effect of a substance on cancer cells. It showed at what point a cancer cell died. Unfortunately, the substance had little effect on the cancer cells. After the depressing news, I learned that it is rare, in Jeff Johnson’s stage of development, for results of an experiment to be successful. Mr. Johnson summarized the hope and then disappointment best when he said, “You know, 95% of our experiments are unsuccessful during the year, but it’s the 5%—the one or two successful experiments, that keep you going.” Leaving Corixa, I was amazed at where Jeff Johnson’s heart was. He is not in cancer research for money or fame. He loves his job because of the potential impact he can have on someone’s life. That is where a true scientist’s priorities should be! • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  7. 7. Holder 7 So what is Cancer? Cancer is a condition, occuring in both plants and animals, when cells multiply too quickly, destroying healthy tissue. In humans, the majority of reported cancer cases are in middle-aged to elderly adults. The most effected areas of the body include the skin, digestive organs, the lungs, the prostate gland, and the female’s breasts. It occurs when chemicals that direct cell growth are damaged, resulting in cells multiplying out of control. Doctors and scientists classify the type of cancer by where it is located in the body and the tissue of origin. There are two kinds of cancer classified as carcinoma and sarcoma. Carcinoma is the more common of the two. It develops in the epithelial tissue. The epithelial tissue is the outer layer of skin and the lining of the surfaces of the internal body and organs. The second kind of cancer, sarcoma, develops in connective tissues. There are also two kinds of genes that control cell growth and division: proto- oncogenes and suppressor genes. Proto-oncogenes promote cell growth and divisions while suppressor genes limit the amount of cell growth. In a perfect scenario, the proto- oncogenes and the suppressor genes check each other. However, when proto-oncogenes are damaged, and overactive form called oncogene can take over. The suppressor genes are damaged, they lose the ability to stop cell multiplication. Traditional Cancer Treatments Surgery, radiation therapy, and drug therapy are the primary treatments for cancer today. With surgery doctors remove the tumor and possibly the healthy tissue around it to prevent spread. An excellent example of this procedure is the mastectomy. When a • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  8. 8. Holder 8 mastectomy is preformed, the surgeon takes not only the tumor, but also the surrounding breast. A major drawback of surgery is the invasiveness needed to be successful and the recovery time. Also, as in the case of mastectomies, psychological effects can take years to overcome. Radiation therapy uses x-rays or other particles from radioactive substances like cobalt and radium. While this form of treatment kills the cancerous cells, it also destroys healthy cells. So, to be effective enough to be beneficial to the patient, radiation therapy must kill more cancer cells than the normal cells. New machines are being used now that target the cancer cells more precisely, thus reducing the number of normal cells damaged. These machines are called the Super Voltage X-Ray and the Cobalt Bomb. Drug therapy, also known as chemotherapy, is the idea that a drug can target rapidly growing abnormal cells. The theory is good, however, blood-forming cells, hair- forming cells, and even the cells lining the intestinal tract are rapidly reproducing. Chemotherapy does not discriminate against healthy cells and cancerous cells—it destroys both as long as they multiply quickly. So, some of the side effects of chemotherapy are hair-loss (when hair-forming cells are killed), nausea and vomiting (from destroying the cells lining the intestines), and infection and anemia (when the blood-forming cells are destroyed). Another kind of therapy called multimodality therapy combines treatments together. For instance, a surgery followed by chemotherapy. The positive side of such combinations is that it can destroy undetected cancer cells in other areas of the body. A New Form of Treatment • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  9. 9. Holder 9 More recently, researchers have found that there are biological response modifiers that can accomplish two different objectives: the first being to increase the body’s own ability to fight the cancer by using immunology and the second is to increase the body’s ability to withstand aggressive drug treatments. One promising type of a biological response modifier is the monoclonal antibody. Antibodies, which are disease fighting proteins, are made by the thousand by the B cell, a white blood cell. They circulate via the blood stream and attach themselves to antigens. When the antibody attaches to the antigen, it acts as a marker essentially alerting the immune system that the cell is infected and must be destroyed. Monoclonal antibodies can be made in a laboratory by combining a cancer cell with a B-cell. This produces the antibodies that attach to the cancer, alerting the immune system to destroy the remaining cancerous cell. The positive impact of the monoclonal antibody is that it can successfully target a cancer cell without destroying the healthy cells surrounding it. Another biological modifier is the interferon. An interferon is a protein that is produced by cells to resist infection brought about by viruses. In some studies it has been shown to prevent the reappearance of cancer. A third kind of biological modifier is interleukin-2, a protein released by some white blood cells that helps to support the growth of other white blood cells. In some kidney cancer patients, interleukin has stimulated the growth of white blood cells that kill cancerous cells. Cancer Immunology Out on the Market Today Herceptin was the first antibody based cancer therapy. It is used to treat HER-2 driven metastatic breast cancer. Herceptin is able to bind to the surface of the tumor • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  10. 10. Holder 10 cells. This, in turn, blocks cell growth so that the cancer cells can no longer multiply at the unhealthy rate. When it attaches to the HER-2 proteins, natural killer (NK) cells then attach to the Herceptin. This allows the cell to be detected as abnormal and thus destroyed by the immune system. Chemotherapy can also be combined with Herceptin to make a more powerful treatment. The chemotherapy destroys the DNA in the tumors, then Herceptin stops the cells from healing themselves. This causes them to die and the tumor’s growth to slow down drastically. Another drug, RITUXAN, is out on the market that treats patients who have B- cell non-Hodgkin’s Lymphoma. It was the first monoclonal antibody (MAb) approved for the treatment of cancer in the United States of America. Rituxan effectively binds to the surface of the CD20 antigen found on the surface of normal and malignant B cells. From there, it recruits the body's natural defenses to attack and kill the marked B cells. Stem cells in bone marrow lack the CD20 antigen so this form of treatment allows healthy B cells to regenerate after treatment and return to normal levels within several months. New Drugs Being Developed by Corixa Melacine is currently in phase III development. It is composed of broken cells from two human melanoma cell lines mixed with Detox adjuvant, which activate the immune system through vaccination. In studies conducted around the country by the Southwest Oncology Group, the Melacine vaccine had demonstrated that it prolongs the time in relapse-free survival in patients with stage II melanoma as compared to those who were not treated with adjuvant therapy. The study included 689 patients chosen at random from 148 sites. This trial is the largest study of cancer vaccine completed to • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  11. 11. Holder 11 date. In order for the FDA to approve Melacine in the United States, it must go through a second phase III clinical trial. Melacine could potentially have a huge impact on skin cancer survival. According to the American Cancer Society, skin cancer is the most common out of all the cancers. Melanoma, a highly lethal form of skin cancer, accounts for only 4 percent of skin cancers, yet it accounts for 79 percent of skin cancer deaths. Another new drug being developed by Corixa is BEXXAR. BEXXAR combines the ideas of radiology and monoclonal antibodies into non-Hodgkin’s lymphoma. NHL is a blood-borne cancer of the immune system. The monoclonal anti-body binds to a specific protein found on the B-cells. It marks the cancer cell to be destroyed by the immune system. At the same time, a radioisotope can target its radiation to the tumor cells so that fewer healthy, normal cells are damaged. The National Cancer Institute estimates that NHL in the United States alone affects over 300,000 people. That number continues to grow. In fact, since the early 1970’s, the rate of NHL occurrence has grown by 80%. On December 17, 2002, Corixa received strong praise from the Oncologic Drugs Advisory Committee. They unanimously voted that BEXXAR was effective in the treatment of chemotherapy- relapsed and refractory low-grade NHL. The date in which the FDA will finish its review of BEXXAR is on May 2, 2003. Conclusion Cancer treatment is headed in a positive new direction. With companies, such as Corixa, developing innovative ways to treat and perhaps cure cancer, one stands in awe of all the possibilities. It makes one wonder what the next innovation will be. The • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  12. 12. Holder 12 number of people potentially affected by these new antibody treatments is staggering. These new methods of therapy are able to reduce the amount of negative side effects of traditional treatments. As a Research Associate in Cancer Immunology, one is at the groundwork of these exciting new technologies. Not only is this career thrilling, it is filled with untold rewards. Bibliography “Cancer.” World Book. 16th ed. 2002 This was a credible source because the encyclopedia is turned to by many for its unbiased definitions. I used the encyclopedia to gain a basic knowledge of cancer. Yount, Lisa. “Radiation and Chemotherapy” Cancer. Lucent Books, 1999. This was a credible source because it was unbiased and just gave basic definitions and examples of cancer treatments. I used the information to write about the traditional forms of cancer treatment. Siegel, Mary-Ellen, M.S.W.. The Cancer Patient’s Handbook. New York: Walker and Company,1986. This was a good source of information because it was especially written for cancer patients. Not only did it give possible side effects, but it also compared the kinds of treatments so patients know what they’re dealing with. I used this book as a compliment to Lisa Yount’s book. “Melacine.” 15 January 2003 I used this website to learn about Melacine and what Corixa is doing. It was used in my report as an example of future monoclonal antibody drugs. I believe the information to be credible because it was given as a press release and the company presented facts and statistics to back its claims. “BEXXAR.” 15 January 2003 http://www.corixa.com/default.asp?pid=cancer_capsule&id=28. I used this website to learn about BEXXAR and what Corixa is doing. It was used in my report as an example of future immunotherapy drugs. I believe the information to be credible because it was given as a press release and the company presented facts and statistics to back its claims. “Herceptin.” 20 January 2003 • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  13. 13. Holder 13 This source is credible because it was the company that makes the drug. It presented information in a factual way with statistics to back up its claims. I used this information as an example of immunological drugs already out on the market. “RITUXAN” 20 January 2003 . This source is credible because is not only because it was given by the company who makes RITUXAN, but it also gives detailed information as to the effects of the drug and the reasons it works (which check with my other research.) I used this information as an example of immunotherapy drugs already out on the market and approved by the FDA. “Hotjobs” 25 January 2003 http:www.hotjobs.com/cgi-bin/job-show?TEMPLATE=htdocs/job-show.html… I used this search engine to find a job description of a research associate. The job that matched my description was one at the John Wayne Cancer Institute in Santa Monica California. I feel that this is a credible source because it is a well known Cancer research program. I used the information I found as the majority of the descriptions of Research Associates in both my report and on my poster. Johnson, Jeff. Personal Interview. February 18, 2003. Jeff Johnson was my mentor. He works at Corixa Corporation as a Senior Research Associate. His job, the fact that he was selected as a mentor through the Biotechnology Expo, and his education all contribute to his credibility. Currently he is working on the early stages of development/research of immunological therapies for cancer. My interview and my time spent with Jeff Johnson at Corixa Corporation is reflected in my report. • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  14. 14. Holder 14 The Groundbreaking Career as a Research Associate in Cancer Immunology Journal • Ashley Holder • Grade 12 • • Ms. Mary Glodowski • Juanita High School • • February 28, 2003 • Notes Research Associate in Cancer Immunology Background/Training: • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  15. 15. Holder 15 ° College degree in Biological Science, Chemistry, Immunology, or Molecular Biology ° Computer Knowledge ° Experience in Radioisotopes ° Experience with Tissue Culture ° Column Chromatography ° Protein Determinates ° Immunoassay (ELISA, RIA, etc.) ° Western Blots ° Experience in Conduct of Pharmaceutical trials Job Responsibilities: ° Preparation and Isolation of Tumor Antigens from Biological Specimens to be used as Reagents to monitor Immune Responses of Cancer Patients’ Sera ° Prepare Solutions ° Perform Biochemical Analysis and Immunological Assays to monitor Antigens ° Research/Develop various Immunological Assays using Reagents ° Record and Log Lab Equipment and Reagents as required for the General Laboratory Practices (GLP) Typical Workday: ° 9-5 job Opportunities for Advancement: ° A Research Associate can become a Senior Research Associate when he/ she has experience for a number of years as a member of a Clinical Team conducting Studies (Phase I-IV) according to Federal Regulations and ICH Guidelines. He/she as a Senior Research Associate, is responsible for writing or supervising the writing of Clinical Reports or Documents. Salary Ranges: ° $30-50 depending on area of country, experience, and company What is Cancer? ° Cells multiply wildly destroying healthy tissue ° Occurs in both Plants and Animals ° Occurs most often in middle-aged and elderly ° Most affected areas = skin, digestive organs, lungs, prostate gland, female breasts. ° Occurs when chemical instructions directing cell growth, are damaged and cells multiply w/o control ° Caused by Genes (inherited) or Environment ° Classified by Body Site and Tissue of Origin ° Most Cancer is Carcinoma ° Carcinoma = develops in epithelial tissue (Outer layer of skin and lines internal body surfaces and organs. ° Sarcoma = develops in connective tissues Genes Controlling Cell Growth and Division ° Proto-oncogenes = promote cell growth/division ° Suppressor genes = limit cell growth/division • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  16. 16. Holder 16 ° When proto-oncogenes are damaged = over-active form called oncogenes ° Scientists have discovered dozens of oncogenes ° When suppressor genes are damaged, the genes’ ability to stop cell multiplication is destroyed. Traditional Cancer Treatments ° Surgery ° Radiation Therapy ° Drugs (Chemotherapy) ° Multimodality Therapy = Combo of treatments Surgery ° Take out tumor and possibly healthy tissue around tumor (like a mastectomy). Radiation Therapy ° Attacks w/x-rays or particles from radioactive substances like cobalt and radium ° Negative Effect: Kills normal cells and cancer cells. To be positively effective, it must kill more cancer cells than normal ° New Machines: Super-Voltage X-Ray and Cobalt Bomb that reduce the # of normal cells damaged. Drug Therapy (Chemotherapy) ° Idea that drug can target cancer through a chemical process that doesn’t occur in normal cells. ° Negative Effect: It damages normal cells that divide rapidly like cancer. These cells include blood-forming cells (Increase Risk of Infection), hair-forming cells (hair loss), and cells lining the intestines (nausea, vomiting). Multimodality Therapy ° Mixture of treatments can destroy undetected cancer cells in organs or other areas of body. ° A common combo is surgery and chemotherapy Biological Response Modifiers ° Increase body’s ability to fight cancer by strengthening natural responses ° Some are Immunotherapies ° Stimulates Immune System to attack Cancer Cells ° Others improve ability to withstand aggressive drug therapy Biological Modifiers ° Monoclonal Antibodies ° Immunotherapy ° Anti-bodies (disease fighting proteins) ° Thousands made by B-cell (White blood cell). They circulate in blood and bind to antigens (Foreign Substances). ° When antibody attaches to antigen, marks it infected and destined for destruction. ° Monoclonal Antibodies are made in a lab by combining cancer cell with B-cell. Produces antibodies that attach to • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  17. 17. Holder 17 cancer cells alerting the immune system to destroy the remaining cancer. ° Positive: ideally won’t kill good cells ° Interferons ° Protein produced by cells to resist infection by viruses ° Has prevented reappearance of cancer ° Interleukin-2 ° Protein released by some white blood cells to support and sustain growth of other white blood cells. ° Kidney Cancer: In some cancer patients, has stimulated growth of white blood cells that destroy cancer cells. Interview Q: What is your typical workday? A: 10-20% Computer work and data analysis. Q: How do Research Associates tie into the drug development process? A: Research associates do the experiments and analyze results to give supervisors the information the final decision as to where to go next. We basically do all the work! Q: How did you decide to become a research associate? A: Well, going to SPU, I didn’t get any financial aid, so I didn’t qualify for work-study programs like most other people. To get in the door, my professor, Ken Moore, was able to get me a job as a lab assistant at the Fred Hutchinson Cancer Research Center. I was able to do my own research project and it just kind of took off from there. • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  18. 18. Holder 18 We did not have a lengthy formal interview, but instead talked while I received a tour of Corixa. My notes and impressions as well as my report reflect our rather casual time together. Impressions of Corixa and Mentorship Experience Arriving at Corixa, I was amazed at the amount of security. To get into the building, I had to call the security desk for them to “buzz” me in. From there I went to the second floor only to find another security measure. I was given a “Visitor” Badge in exchange for my car keys and told to wait while my mentor, Jeff Johnson, was called. As we made our way to Jeff Johnson’s work area, I was amazed at the company. We passed through a hallway where the supervisors worked, (they had their own offices) passed a group of men eating their lunches outside and entered the large room with 20 different lab/work stations. Everyone was diligently doing his or her research and experiments. Shelves were labeled with employee names and chemicals and white lab coats were flung over the backs of most seats. We sat down at Jeff Johnson’s work area and I immediately noticed his open container violations. I thought to myself, “Wow, Mrs. Glowdowski has taught me well!” We started the interview, but weren’t really sure what to talk about. I asked the basic questions, but we both lost interest quickly. At the end of the abbreviated interview, Mr. Johnson gave me a tour of the lab. He showed me where the CHO was being processed and the different floors. The lab areas on both floors were almost identical, except for the • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
  19. 19. Holder 19 personal touches of family portraits and pictures that adorned many workstations. Jeff Johnson showed me the many cell samples and chemicals being kept in the refrigerators and explained what their purposes were. He seemed impressed that I knew the basic ideas as to what he was explaining. Apparently, a couple of weeks earlier, he had had another student who had not comprehended his explanations. After learning the basics in the theory of cancer immunology, I was given the opportunity to watch one of his experiments be processed. Jeff Johnson, his supervisor, and I all went into a smaller room with a machine that processed some samples. The cancer cells being processed were tested as to the substance that killed them. Unfortunately, the results were not promising. After the experiment was processed, I had to leave. Jeff Johnson showed me out (I had no idea where I was and needed and employee card to get through most of the doors) and we talked about college and things unrelated to cancer immunology. Jeff Johnson was a great mentor. He, like most of the other employees at Corixa Corporation, was very informative. He seemed to really love his job and was good at it. • Ashley Holder • Grade 12 • Juanita High School • February 28, 2003