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118/2/2015 Cancer & the Immune System Hugh B. Fackrell
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228/2/2015 Cancer & the Immune System l Assigned Reading l Content Outline l Performance Objectives –Key terms –Key Concepts l Short Answer Questions
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338/2/2015 Assigned Reading l Janis Kuby’s Immunology 4th Ed Chapter: 22 pp 539-561 l Janis Kuby’s Immunology 3rd Ed l Chapter: 24 pp 573-596
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448/2/2015 Content Outline l Origins & Terms l Malignant Transformation l Tumours of the Immune System l Tumour Antigens l TATAs on human melanomas l Immune Response to Tumours l Tumour Evasion of Immune Response l Cancer Immunotherapy
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558/2/2015 Origins & Terms
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668/2/2015 Benign vs malignant
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778/2/2015 Distribution of Cancer
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888/2/2015 Growth of Breast Cancer Diameter of Tumour (mm) Tumour Cell doubling Tumour visible by X rays Tumour first palpable Death of Patient 10 8 cells 10 9 cells 10 12 cells
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998/2/2015 Altered Growth Properties
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10 8/2/2015 Localized Benign Tumour
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11 8/2/2015 Tumour Invasion of Basal Lamina
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12 8/2/2015 Metastasizes to Other Sites
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13 8/2/2015 Tumour Antigens l Tumour specific Antigens –chemically induced –virally induced l Tumour associated antigens –oncofetal tumour antigens –oncogene proteins
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14 8/2/2015 TSTA vs TATA
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15 8/2/2015 Radio labelled anti CEA
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16 8/2/2015 Genes for TSTAs
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17 8/2/2015 Malignant Transformation l Oncogenes l Induction of cell proliferation l Inhibition of cell proliferation l Regulation of apoptosis
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20 8/2/2015 Chromosomal translocations
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21 8/2/2015 Tumour Induction
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22 8/2/2015 Induction of Tumours
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23 8/2/2015 Tumours of the Immune System
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25 8/2/2015 TATAs on human melanomas
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26 8/2/2015 TATAs on human melanomas
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27 8/2/2015 Immunity to Polyoma virus(1)
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28 8/2/2015 Immunity to Polyoma virus(2)
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29 8/2/2015 Immunity to Polyoma virus (3)
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30 8/2/2015 Immunity to Polyoma Virus (4)
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31 8/2/2015 Immune Response to Tumours l NK cells & macrophages l Immune surveillance theory
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34 8/2/2015 Tumour Evasion of Immune Response l Immunologic enhancement l Modulation of tumour antigens l Reduce MHC-I l No co-stimulatory signal
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37 8/2/2015 Tumor Escape
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38 8/2/2015 Cancer Immunotherapy l Modify Co-stimulatory signal l Enhance APC activity l Cytokine therapy l MABs l Tumour cell vaccines
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39 8/2/2015 Cancers Treatable by Bone Marrow Transplants Allogenic/syngenic Transplant –Breast cancer –aplastic anemia –leukemia –ALL –CML –Myeolodysplasia –multiple myeloma –Non- Hodgkin’s lymphoma –Hodgkin’s disease Autologous Transplants –Leukemia –AML –ALL –Multiple Myeloma –Non Hodgkin’s lymphoma –Hodkin’s disease –Solid tumours –Breast –ovarian –testicular –Neuroblastoma
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40 8/2/2015
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41 8/2/2015 Transfect co stimulartory signal
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42 8/2/2015 Transfect with GM-CSF
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43 8/2/2015 Lak cells & IL-2
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44 8/2/2015 Mabs to B cell Lymphoma
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45 8/2/2015 Tumour Cell Vaccine Immune Response to MCA or PV Transplant killed cells of MCA induced sarcoma A l Challenge with Sarcoma A- No Growth l Challenge with Sarcoma B- growth Transplant killed cells of Polyoma Virus induced sarcoma A l Challenge with sarcoma A no growth l challenge with sarcoma B no growth l SV40 induced sarcoma C- growth
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47 8/2/2015 DONE!!!
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60 8/2/2015 Performance Objectives
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61 8/2/2015 Key Terms l antibody dependent cell mediated cytotoxicity (ADCC), benign tumour, cancer, l carcinogens, proto oncogens, immune surveillance, Specific immunotherapy, l non specific immunotherapy, immunotoxins,Lymphokine activated killer cell(LAK),
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62 8/2/2015 l neoplasm, oncofetal antigens, oncogens, tumour, tumour associated antigens, l tumour associated transplantation antigens, tumour specific antigens, l tumour specific transplantation antigens
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63 8/2/2015 Key Concepts l Differentiate between a benign tumour and a malignant tumour. l Describe the concept of immunosurveillance l Describe the different ways that tumours can camouflage themselves to evade immune defenses, l Discuss the advantages of immunotherapy over other forms of cancer therapy.
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64 8/2/2015 l Distinguish between specific and nonspecific immunotherapy with the use of specific examples. l Describe immunotoxins. l Describe the development of humanized antibodies to tumour antigens l Evalulate the contribution of T cells, NK cells, Macrophages, and B cells to tumour immunity.
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65 8/2/2015 l Distinguish between tumour specific transplantation antigens and tumour assoicated transplantation antigens. l Describe oncofetal antigens.
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66 8/2/2015 Short Answer Questions
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67 8/2/2015 l Explain how some cancer cells that can make TGF-beta are immunosuppressive. l Tumours and transplants are similar to one another,yet very different. Explain this observation in the context of what the immune system recognizes and the result of this recognition. l The qualities of proliferation and differentiation are essentially all that distinguishes a normal cell from a cancer cell. Explain.
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68 8/2/2015 l Design an experiment using mice that proves that the immune system provides immunity against tumours. l Distinguish between tumour-specific transplantation antigens (TSTA) and tumour associated transplantation antigens (TATA). l Design an experiment to show Tumour associated Transplantation Antigens (TATA). l What is the main difference separating cell surface antigens from chemically induced and virually induced cancers?
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69 8/2/2015 l Speculate on why this difference leads to difficulty in designing anticancer vaccines. l What are oncofetal antigens? Are they important in tumour immunity? Why? l What is immune surveillance? l All evidence for immune surveillance is indirect. Speculate on how you could get direct evidence.
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70 8/2/2015 l What immune cells play a role in tumour rejection? Briefly describe how each accomplishes this task. Include such things as cytokines, perforins, ADCC etc. l Cancers camouflage themselves to evade antitumour defenses. Pick three possible forms of camouflage that you think are most important, describe them and state why you think they are most important. l What are immunotoxins?
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71 8/2/2015 l Surgery, radiation and chemotherapy are the methods most widely used to treat cancer patients. What are the problems with this regimen, and how could immunotherapy overcome these problems. l Distinguish between specific and nonspecific immunotherapy.
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