6. 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.
17. • Concordant xenografting
– transplantation between closely-related
animal species (baboon-to-human)
• Disconcordant xenografting:
– Transplantation between distantly-related
species (pig-to-human)
18. • 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
21. 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.
22. • 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
23. • 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
24. • 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
25. • 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
26. 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
27. 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
29. • 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
30. 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)
31. 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
32. 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
33. Ethical Issues
• Physical discomfort
• Psychological
discomfort
• Why should animals
suffer for humans?
• The right to life
Animal Rights
34. Ethical Issues
• Bible technicalities
• Importance of human
life
• Pigs are already
slaughtered daily
• Use as few primates
as possible
Arguments For Xenotransplantation