Difficult for me to comment...... first, I have the highest regard for the SAB of Diacrin. Couldn't respect them more, across the board.
But..... not to worry. This "masking" is very much being misrepresented, IMO, by Diacrin.
"Blocking antibodies" have been tested in allo and xenotransplantation models since 1970. I used to sit and watch Yoko Mullen do this work on a daily basis, as I was mucking with MCA-induced sarcomas and various other stuff in the same surgery room.......
Transplantation 1977 Aug;24(2):99-105
Cytotoxic versus immunoblocking effects of specific alloantibodies: effects of
IgM, IgG, and IgG2 on rat kidney allograft survival.
Mullen Y, Raison R, Hildemann W
Passively introduced IgM alloantibodies of antidonor specificity regularly led to decreased kidney allograft survival times,
whereas IgG alloantibodies from the same hyperimmune sera had a specific immunoblocking effect that promoted prolonged
allograft survival. These strikingly opposite effects as a function of antibody isotype occurred across both strong H-1 (Ag-B)
and moderate non-H-1 histocompatibility barriers. However, IgM and IgG directed against non-H-1 specificities were far
more effective, respectively, in either curtailing or prolonging renal allograft survival. In the Fischer to Lewis strain combination,
this was reflected in a 4-fold diminution in median survival time of IgM-treated recipients from 115 to 31 days, in contrast to
indefinitely prolonged survival of IgG-treated recipients (greater than 350 days). Purified IgG2 alloantibodies proved as
effective as the whole IgG fraction in passively promoting long-term renal allograft survival across a strong H-1 barrier.
Conflicting data from other sources is evaluated. Possible mechanisms of specific immunoregulation are briefly discussed in
relation to antibody properties of specificity, idiotype, class-subclass, and avidity-affinity.
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Next breath...... a ton has been learned about antibody structure and function in the past 20 years, and Diacrin is doing great work. However, I do NOT feel that this technology is ready for prime time anywhere other than behind the blood brain barrier, and perhaps not even there.
Note the coauthors.......
Int J Cancer 1977 Nov 15;20(5):748-58
Immunity to MCA-induced rat sarcomas: analysis of in vivo and in vitro
results.
Harmon RC, Clark EA, Reddy AL, Hildemann WH, Mullen Y
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Here's a description of what I believe that Diacrin is talking about.......
J Immunol 1999 Jun 15;162(12):6993-7001
Human anti-porcine T cell response: blocking with anti-class I antibody leads
to hyporesponsiveness and a switch in cytokine production.
DerSimonian H, Pan L, Yatko C, Rodrigue-Way A, Johnson E, Edge AS
Department of Molecular and Cellular Biology, Diacrin, Inc., Charlestown, MA 02129, USA. harout@diacrin.com
Intervention in the molecular interactions that lead to an immune response is possible at various stages of Ag recognition and T
cell activation. Perturbation of the interaction of the TCR with the MHC/peptide ligand complex is one approach that has
shown promise for autoimmunity and graft rejection in blocking T cell-activated responses. In this study, we investigated the
effect of altering the target MHC class I molecule by blocking with Abs. We established a system that analyzed the human T
cell response against MHC class I+/class II- porcine stimulatory cell targets. The primary human response against porcine
smooth muscle cells was CD8+ T cell dependent. In the presence of F(ab')2 fragments of the MHC class I-reactive Ab,
PT-85, the proliferative response was inhibited and production of IL-2 and IFN-gamma was blocked. Moreover, in a
secondary response, proliferation was reduced and type 1 cytokine levels were inhibited. In contrast, levels of IL-10 and IL-4
were sustained or slightly increased. These findings indicate that Ab against MHC class I blocked the recognition of porcine
cells by the human CD8+ T cells and altered the cytokine secretion profile. Thus, a single treatment with PT-85 F(ab')2
directed against the MHC class I molecule provides an attractive approach to the induction of T cell tolerance that may provide
long-term graft survival in porcine-to-human cell transplantation.
************
I just plain, flat out, do not believe that this will work. And, no, I'm not impressed with the use of F(ab')2.... nothing new about that concept. Think about it..... why haven't similar procedures been used for human allotransplantation of kidneys for the past 20 years?
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