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Printable Handouts
Navigable Slide Index
- Introduction
- Short-term treatment for a long-term benefit
- Tolerance can be induced in the adult
- Antibodies & induction of therapeutic tolerance
- Immune system, tolerance, regulation
- Tolerance, co-receptor, co-stimulation blockade
- Regulatory T-cells in transplantation tolerance
- TGFβ signalling in T-cells
- Transgenic mice & reductionist opportunities
- “Knock-in” mice with a human CD2-CD52
- Foxp3+ pTreg Cells Develop in Tolerant Animals
- Foxp3+ pTreg cells develop in tolerant animals
- iTreg cells don’t reject grafts but regulate in vivo
- Tolerance depends on vigilance by FoxP3+ Treg
- Foxp3 - sufficient graft rejection suppressor (1)
- cFoxp3-transduced T-cells regulate in vitro
- Foxp3 - sufficient graft rejection suppressor (2)
- Foxp3+ iTreg cells prevent graft rejection
- Events in the tolerated tissue
- Tolerated grafts contain cells that can reject
- Tolerated grafts rejected after targeting
- Tolerated grafts are still retained after treatment
- TGFβ & anti-inflammatory adenosine
- TGF-β induces CD73 expression
- Suppression by TGFβ iTregs is AMP-dependent
- Essentials amino acids & mTOR inhibition
- Induction within dendritic cells
- Acquired immunological privilege
- Conclusions
Topics Covered
- Short-term treatment for a long-term benefit
- Antibodies and induction of therapeutic tolerance
- Coreceptor and costimulation blockade during antigen recognition
- Regulatory T-cells in transplantation tolerance
- Transplant models and transgenic mice
- Immunologically privileged microenvironments
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Waldmann, H. (2019, April 30). Monoclonal antibodies to induce therapeutic immunological tolerance [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 14, 2024, from https://doi.org/10.69645/ZUDJ9157.Export Citation (RIS)
Publication History
Financial Disclosures
- Herman Waldman has ownership interests in the Absolute Antibody company.
A selection of talks on Immunology & Inflammation
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Herman Waldmann from the Department of Pathology, Oxford University.
I'm going to be talking about
therapeutic antibodies for the induction immunological tolerance.
0:12
All of you will be familiar with the notion
of short-term treatment from long-term benefit.
This was a notion applied to drugs using penicillin to treat bacterial infections,
and very hard to imagine that one would want to give penicillin for
life to treat an illness that is debilitating.
The attraction of antibiotics was of
course the market gives them for a few days and cure.
Yet, when come to a whole range of immunological diseases,
we find ourselves with the drug industry providing
treatments that many people have to take
indefinitely for long periods and they costs a lot of money.
Why are they not drugs that can be given short term
for long-term benefit in diseases like multiple sclerosis,
kidney transplantation, type one diabetes,
rheumatoid arthritis, and so on.
Why are we giving drugs that lasts and have to be given forever?
Well, of course there are number of reasons.
Some as we haven't found such treatments yet.
Second, perhaps a little more disturbing is the possibility that
commercial organizations can't see a business
in giving drugs short-term for long-term benefit.
I'd hate to imagine that that was true, and thirdly,
there may be there hasn't been a business plan generated that will enable
short-term treatment to be attractive to pharmaceutical companies today.
If whether we can find ways of manipulating
the immune system to enable it to become tolerant of transplants,
and become tolerant again to autoimmune disorders,
like Multiple Sclerosis and diabetes,
and what are the principles that underlie the generation of such tolerance?
I'm going to be using his probes antibodies that target molecules of the immune system,
and I'm going to show you that we can with antibodies in rodents,
give short-term treatments to get long-term benefits that
stop unwanted immune responses using transplantation
as my model system but such principles could easily apply to
autoimmune diseases and other forms of chronic immune pathology.