antibody engineering and xenotransplantation

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power point of those student who have their biotechnology :)) goodluck and goodbless..

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antibody engineering and xenotransplantation

  1. 1. Antibody Engineering By : Karla Mae M. Manalo Bachelor of Arts in Mass Communication Major in Journalism 2- A
  2. 2. Antibody • A blood protein produced in response to and counteracting a specific antigen
  3. 3. Antibody Engineering • antibodies are designed, assembled at the molecular level and utilized to achieve specific functions in biological systems
  4. 4. Two immunoglobulin •lg light chain •lg heavy chain
  5. 5. Antibody Engineering – The Fc or Fab parts are manipulated for modifying binding affinity and specificity, while the Fc part is manipulated with the porpose of manipulating effector-functions of the antibody.
  6. 6. Papain Fc Fab
  7. 7. Antibody Generation
  8. 8. Figure 2-15 part 1 of 2 CDR1 and CDR2 CDR3
  9. 9. CDR1 and CDR2 CDR3
  10. 10. Xenotransplantation
  11. 11. Xenotransplantation • Xenotransplantation refers to the practice of transplanting, implanting, or infusing living cells, tissues or organs from one species to another
  12. 12. • Concordant xenografting – transplantation between closely-related animal species (baboon-to-human) • Disconcordant xenografting: – Transplantation between distantly-related species (pig-to-human)
  13. 13. • Pigs have larger organs • Pigs are already slaughtered every day for meat • Primates have smaller organs • Primates share most of our genetic make up • Primates are not available in numbers Primates vs. Pigs
  14. 14. Types of Xenotransplant
  15. 15. Advantages • It saves human lives. • It solves donor organ shortage.
  16. 16. History of Xenotransplantation • 1682 – Bone from a dog was used in Russia in an attempt to repair his injured skull. This attempt was reported successful, but the Russian had the bone removed soon after surgery under threat of the church of excommunication. • Late 1800’s – Frog skins were often used as a way of healing burns or skin ulcers by grafting said skin directly onto the patient’s skin. • 1905 – French Surgeon grafts kidney tissues from a rabbit into a child, the child died two weeks later • 1920 – Doctor Serge Voronoff transplanted tissues from the testicles of monkeys into older men, claiming that the procedure brought sexual rejuvenation.
  17. 17. • 1963-64 – Thomas Starzl grafts baboon kidneys into six patients. The patients only lasted between 19 and 98 days. • 1963-64 – 12 patients received Chimpanzee kidneys , however, most failed within two months of the surgery, though one did live for nine months! • 1964 – A 68-year-old man dies two hours after receiving a Chimpanzee heart. • 1969-74 – Chimpanzee livers were transplanted into three children. They only survived between one to fourteen days. • 1977 – A 25-year-old woman receives a baboon heart but dies only six hours after surgery. About the same time a 60-year- old man receives a chimpanzee heart to assist his own heart, but dies four days after. History of Xenotransplantation
  18. 18. • 1984 – Baby Faye receives a baboon heart and dies 20 days later. • 1992 – Using a four-drug “cocktail” to assist the transplantation of a baboon liver a patient lives for 71 days. However, the patient died of a brain hemorrhage and the type of rejection typical was not seen. History of Xenotransplantation
  19. 19. • 1992 – A pig liver was placed besides the patients own liver in hopes that the extra liver would assist the patient’s liver long enough for a human donor to be found. The patient died after 32 hours. • 1993 – Baboon marrow and kidney transplant, patient dies after 26 days. • 1995 – Immune cells from a Baboon used for an AIDS patient. Condition improved though cells died quickly. • 1997 – Pig fetal nerve cells used in patients with Parkinson’s disease. Pig cells survived in one patient for over 7 months History of Xenotransplantation
  20. 20. • The Need for Organ Donors grows at 15% per year – about 60% of patients awaiting replacement organs die on the waiting list • 2004 Australia – In a survey two- thirds say they would use an animal organ to save their life – Survey shows 7 out of 10 males, and 6 out of 10 females would agree to xenotransplantation Statistics
  21. 21. Biological Concepts • Transplanted animal cells to be used for hemophillia, diabetes, Alzheimer’s and Parkinson’s disease • Organ Transplants • A Way of delivering genes of therapeutic importance Modern Uses
  22. 22. Biological Concepts • 25 known diseases can be contacted from pig to human • Public Health risks • Perfection of Cloning • Rejection rate is higher Existing Problems and Worries
  23. 23. Problems
  24. 24. • Rejection of the xenograft is thought to occur, since galactose - 1,3-galactose is expressed by pig cells. • Humans are known to produce antibodies against this protein
  25. 25. Solutions • Interruption of the complement cascade • The recipient's complement cascade can be inhibited through the use of cobra venom factor (which depletes C3), soluble complement receptor type 1, anti-C5 antibodies, or C1 inhibitor (C1-INH)
  26. 26. Solutions • Transgenic organs (Gen engineered pigs) – 1,3 galactosyl transferase gene knockouts – deletion of gene which codes for the enzyme responsible for expression of the immunogeneic gal-α-1,3 Gal moiety – Increased expression of H-transferase (α 1,2 fucosyltransferase), an enzyme that competes with galactosyl transferase – Expression of human complement regulators (CD55, CD46, and CD59) to inhibit the complement cascade
  27. 27. Ethical Issues • Jewish – Forbidden to eat any part of a pig • Heart is the seat of the soul • No hybridization of man with any other species Religion
  28. 28. Ethical Issues • Physical discomfort • Psychological discomfort • Why should animals suffer for humans? • The right to life Animal Rights
  29. 29. Ethical Issues • Bible technicalities • Importance of human life • Pigs are already slaughtered daily • Use as few primates as possible Arguments For Xenotransplantation

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