Harold.....
as you know, I don't pay much attention to companies that actually sell stuff. However, here's something to further torture you........
315
HIGH LEVELS OF STABLE MULTI-LINEAGE HEMATOPOIETIC
CBIMERISM AND DONOR-SPECIFIC ALLOGENEIC SKIN GRAFT
TOLERANCE WITH T-CELL COSTIMULATORY BLOCKADE
Background: The induction of mixed hematopoietic chimerism by bone marrow transplantation leads
to donor-specific tolerance if host T-cells are adequately depleted during conditioning. Because of its
potential toxicity in the chemical setting, we sought to avoid T-cell depletion in the host conditioning.
Methods: C57BL/6 mice received a non-myeloablative dose of 3Gy whole body irradiation (do) and
were injected with 15x10^6 fully MHC-mismatched, unseperated bone marrow cells from B10.A
donors on the same day. In addition, hosts were injected with a single dose of an ant+CD40L
antibody (MR1; 0.45mg/mouse) and CTLA4Ig (0.5mg/mouse) either alone or in combination on d0
and d+2, respectively. A control group received anti-CD4 and anti-CD8 T-cell depleting antibodies
on d-5 and d-1. Donor chimerism in peripheral blood was followed by flow cytometric analysis at
multiple time points, and donor and third party (A.SW) skin grafts, were placed 3-10 weeks after
bone marrow transplantation. Results: Treatment with the combination of MRI plus CTLA4Ig led to
high levels of multi-lineage chimerism (>40% donor cells in the T-cell, B-cell and myelold lineages)
that was sustained throughout the observation period of more than 7 months. MRI alone, in contrast,
led to initially high levels of donor representation, which, however, were not stable over time.
Treatment with CTLA4Ig alone did not result in chimerism detectable by flow cytometric analysis.
MRI plus CTLA4Ig led to indefinite donor skin graft survival (>lOO days in 12 of 14 mice), while
third party grafts were rejected within 2 weeks. In the control group receiving T-cel1 depleting
antibodies, 3 of 5 donor grafts survived for 100 days. CTLA4Ig alone did not permit prolonged skin
graft survival. MRI alone prolonged survival, but 7 of 9 grafts were rejected before day 100.
Conclusion: Treatment with anti-CD40L antibody plus CTLA4Ig allows the induction of high levels
of stable mixed chimerism and skin graft tolerance without T-cell depletion or myeloablation of the
host
T Wekerle, MH Sayegh, J Hill, A Chandraker, KA Swenson, G Zhao and M Sykes. Transplantation Biology
Research Center/Massachusetts General Hospital and Laboratory of Immunogenetics and
Transplantation/Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02129, USA
*****************
So, how in the world to you sell stock in a company that has anti-CD40L coming along?
:-)
BTW.... for those who are watching this issue, yes, that's the BTRN-alligned crew. The CD2 epitope defined by 507 is only expressed on human, gorilla and chimp, so this study doesn't worry me from that stand. I do not know if there's a potential to sneak through with an anti-CD40L-related use patent for this application (human chimeras). |
