P-T RESEARCH HIGHLIGHTS
"New drug may mean freedom for transplant patients"
(courtesy Wisconsin Regional Primate Research Center)

A new drug prolongs the survival of transplanted kidney tissue when
it is administered on the day of transplantation in rhesus monkeys,
a University of Wisconsin-Madison study shows.

The new drug might eventually free organ transplant patients from
taking toxic drugs for the rest of their lives.

Stuart Knechtle, M.D., transplant surgeon at University of
Wisconsin Hospital and Clinics in Madison, Wisconsin, tested the
effect of giving immunotoxin FN 18-CRM9 to rhesus monkeys. The
treatment, begun on the day of transplantation, prolonged the
survival of transplanted kidney tissue in all groups of treated
rhesus monkeys. However, there were limits to the development of
long-term tolerance to the transplanted tissue. Tissue loss between
50 and 135 days after transplantation was most often due to
interstitial nephritis, or inflammation of the kidney tissue. Later
tissue loss was due to chronic rejection.

Knechtle also evaluated the effect of immunotoxin on antibody
production. In measuring the ability of treated monkeys to develop
antibodies, he found that they had intact antibody responses to
alloantigen, tetanus, diphtheria and xenoantibody. 

He and his colleagues also evaluated the effect of immunotoxin on
T lymphocyte cell recovery. CD4 cells recovered gradually over six
months. T lymphocyte cell-dependent B-cell responses remained
intact after treatment.

In a previous study with rhesus monkeys, Knechtle found that
immunotoxin treatment seven days before transplantation also
resulted in tolerance to the transplanted tissue. The drug works
by destroying the T lymphocyte cells that recognize foreign organs.
When the T lymphocyte cells repopulate the body, Knechtle thinks,
they accept the new organ as part of the body and do not work to
reject it. It was after this study that Knechtle developed the hope
that the new drug would eventually free future transplant patients
from taking drugs all their lives. 

Knechtle also hopes to develop a one-time drug treatment that will
stop the need for past transplant patients to continue taking drugs
every day. He also hopes that immunotoxin will reduce the necessity
of trying second and third transplants on people who reject their
initial donor organs.

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For more information, please contact Dr. Knechtle at
stuart@tx.surgery.wisc.edu.

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References:
Knechtle, S.J., J.H. Fechner, Jr., Y. Dong, S. Stavrou, D.M.
Neville, Jr. T. Oberley, P. Buckley, N. Armstrong, K. Rusterholz,
X. Hong, M. Tsuchida, M.M. Hamawy. 1998. Primate renal transplants
using immunotoxin. Surgery. Aug. 124(2):438-446.

Fechner J.H., Jr., D.J. Vargo, E.K. Geissler, C. Graeb, J. Wang,
M.J. Hanaway, D.I. Watkins, M. Piekarczyk, D.M. Neville, Jr., S.J.
Knechtle. 1997. Split tolerance induced by immunotoxin in a rhesus
kidney allograft model. Transplantation. May 15;63(9):1339-45.

Knechtle S.J., D. Vargo, J. Fechner, Y. Zhai, J. Wang, M.J.
Hanaway, J. Scharff, H. Hu, L. Knapp, D. Watkins, D.M. Neville, Jr.
1997. FN18-CRM9 immunotoxin promotes tolerance in primate renal
allografts. Transplantation. Jan 15;63(1):1-6.

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P-T Research Highlights appears every other week and focuses
broadly on research involving non-human primates. Coverage includes
biomedicine, behavior, conservation and veterinary science. Please
submit highlights for this column to Larry Jacobsen, P-T Research
Highlights editor, at jacobsen@primate.wisc.edu. A 300-word limit and
lay-language style are recommended. P-T Research Highlights are
supported by a grant from the National Institutes of Health,
National Center for Research Resources.  Copyright 1998,
Wisconsin Regional Primate Research Center. No portion of this highlight
may be copied or redistributed without the consent of the editor.

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