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Moditope ... From the Scancell archives
CD4 responses are highly clonal and showed TEMRA (highly cytotoxic
effector memory cells) or effector memory phenotype.
? Some donors showed a pre-existing (memory) responses to
citrullinated peptides.
? Repertoire to citrullinated peptides exists in cancer patients that
could potentially be boosted by immunization to assist in tumor
eradication.
Abstract
The expression of CD45RA is generally associated with naive T cells. However, a subset of effector memory T cells re-expresses CD45RA (termed TEMRA) after antigenic stimulation with unknown molecular characteristics and functions. CD4 TEMRA cells have been implicated in protective immunity against pathogens such as dengue virus (DENV). Here we show that not only the frequency but also the phenotype of CD4 TEMRA cells are heterogeneous between individuals. These cells can be subdivided into two major subsets based on the expression of the adhesion G protein-coupled receptor GPR56, and GPR56+ TEMRA cells display a transcriptional and proteomic program with cytotoxic features that is distinct from effector memory T cells. Moreover, GPR56+ TEMRA cells have higher levels of clonal expansion and contain the majority of virus-specific TEMRA cells. Overall, this study reveals the heterogeneity of CD4 TEMRA cells and provides insights into T-cell responses against DENV and other viral pathogens.
https://www.nature.com/articles/s41467-017-01728-5
so as i have explained before .... Immunobody generates T cells that are Potent, indeed hIgh avidity T cells are deleted before they are released by the thymus
""""To gain immune recognition, the tumour must present an epitope that has avoided thymic regulation and binds with higher affinity than the self epitopes. This could be a neo-epitope which is
formed by a mutation that occurs during oncogenesis, cancer-associated viral epitopes or post translationally modified epitopes. Moreoccasionally, there are epitopes from self antigens that have avoided thymic deletion."""""""""""
I suspect the reason why they don't use Immunobody ........... the immunogenicity of the citrullianted peptide is to high
Your thoughts burble
Yes sad.Remember it was a huge site and only visited a couple of times for licensing discussions but had friends who worked there but way before your time I am sure lol
Yup, was a lovely site. Such a shame Pfizer had a poor track record in their R&D sector during Ian Read's tenureship. Very short sighted decisions were made which cost the company - one was the loss of the Sandwich site.
Lindy has stated in the past she can use Immunobody .......... indeed the very specific points was one of the reasons why they split the patent. modtopes peptides are still taken up by Dendritic cells, are you saying that CD4 can differentiate into Killer Cells by this interaction with the DC's or do with have a natural Repertoire of them ... Lindy can differentiate in Vitro .. i believe the TSCM's can differentiate also which is why Mab 2811 is of such interest ...
Great entrepreneurIal skills Burble. Presumably you were down in Sandwich.
lol yes was about to say the same - a scientist with an entrepreneurial spirit, excellent and no wonder you've invested in Scancell :)
Great story Burble - love the entrepreneurial spirit in you!
Bermuda
Labs run of coffee. You should see the panic in a department when the coffee machine breaks! Just after they announced we were being put on redundancy notice at Pfizer, they closed all the on-site coffee shops within weeks! Every single meeting was done over a coffee (if you organised the meeting it was expected you would buy coffees) and the panic that spread across site was pretty funny to watch.
Entrepreneurial me realised there was a gap in the market, went to Argos and purchased 10 filter coffee machines and dotted them over site with honesty boxes. Cost of a bag of coffee from Asda was around £2 a day per machine. The honesty boxes were making upwards of £50 a day....was a tidy little profit maker for the last three months of my contract there!
AB124
Thanks for the kind words but the only role I could ever perform in any scientific forum would be to fetch the coffees.
'Why did they chose only to run with a peptide vaccine ... ?'
My guess is a very simple reason.
- Immunobody - amino acid target.
- Moditope - amino acid target with post-translational modifications
Post-translational modifications are difficult to encode within a DNA construct in the lab (requires many modifications and additions to expression systems). Impossible to do in vivo. Hence PTMs required for moditope to work cannot be encoded within a DNA based vaccine, hence the need to go down the peptide route.
lol ...
He also told you he was a Property Developer
he also told you he was a "Financial advisor"
he also told you "precious metals are not commodities"
and No offence Ivy ... put you also posted that following Tosh's trading policy was the best course of action ... indeed you followed it to the letter .. you sold down Scancell
Yes AB thanks for pointing out what a balanced and polite way to discuss a scientific paper without falling out.
PS for clarification it was me that referred to Tosh as an “expert” but explicitly and specifically refers g to his CFDs operate and in connection with no other area.
FYI he worked as Head of a CFD Dept in the City for 30 years so may have had a particular insight when clarification was needed to rectify a misunderstanding.
I would not have replied fear of being accused of trying to stir up things but I will respond to clear ,is representation of my previous posts.
ATB
on moditope
well that's the problem, its not a scientific forum and mistakes explaining things lead to shareprice movements especially if a party is Elevated as some sort of Expert .......... which is why i said be very careful pushing a Poster to the forefront, Bermuda has had experience of this despite him saying that he is not an expert. Its far better to engage in getting others to think about why ...
so lets try again ...
Scancell as in house the capacity to invoke High Avidity T cells .. via the Immunobody Platform .. why did they chose only to run with a peptide vaccine ... ?
Burble and Bermudashorts
Not wanting to speak out of turn, but what a great way to sort out a slight misunderstanding.
A textbook example of a difference of opinion graciously and politely explained and put to bed.
It looked almost like a scientific forum (to the untrained eye like mine anyway).
Thanks for showing me how it should be done!
No problems.
That makes sense. I apologise! I read so many manuscripts with work that it all blends into one at times!
Burble,
No, this was my original post on 27th August when I posted a link to the research paper but as you can see thought it all looked a bit beyond my paygrade:-
Bermudashorts
No Opinion
Scancell - Glycans14 Aug 2020 09:57
Following on from my previous post, yet more research on the FG88 glycan has been published today, this time involving researchers from RMIT University, Australia.
The paper, 'Molecular and structural basis for Lewis glycan recognition by a cancer-targeting antibody' was published in the peer-reviewed Biochemical Journal. Haven't had a chance to download the full pdf. and suspect that it's way beyond my level of understanding in any case. However, further evidence that plenty is going on with these mAbs.
https://portlandpress.com/biochemj/article/doi/10.1042/BCJ20200454/226072/Molecular-and-structural-basis-for-Lewis-glycan
You then posted a great explanation of the different types of mAb to which I replied on 9th September:-
Bermudashorts
Posted in: SCLP
RE: Glycan mAbs - Burble09 Sep 2020 14:20
Burble
Have finally had a chance to read and take in your post last night on the difference between chimeric and humanised mAbs and it's starting to make sense so thanks very much! Also helped to visualise the different types of antibody and the diagrams in the link below were useful alongside the one in your post.
Going to use your post to now go and have another read and try to understand more from Scancell's recent paper 'Molecular and structural basis for Lewis glycan recognition by a cancer-targeting antibody'
https://absoluteantibody.com/antibody-resources/antibody-engineering/humanisation/
https://portlandpress.com/biochemj/article/doi/10.1042/BCJ20200454/226072/Molecular-and-structural-basis-for-Lewis-glycan
I thought that was in relation to this paper https://cancerres.aacrjournals.org/content/80/16/3399 and the corresponding RNS https://www.lse.co.uk/rns/SCLP/publication-highlights-potential-of-avidimab-hl98138qyipcdc0.html, unless i am wrong this looks to be a new publication which goes into more detail about the molecular mechanisms behind the FG88.2 and chimeric ch88.2 mAbs.
Burble/billbrown
Yes, that research was posted on the bb a few weeks ago and was the reason I asked about the difference between murine, chimeric and humanised antibodies. Easier to make sense of it once you understand that (only slightly though!).
A very interesting read, especially the comparison between the murine and the chimeric antibodies and the differences these are presenting at an experimental level.
Molecular and structural basis for Lewis glycan recognition by a cancer-targeting antibody
....... Lindy G. Durrant
https://portlandpress.com/biochemj/article-abstract/477/17/3219/226072/Molecular-and-structural-basis-for-Lewis-glycan?redirectedFrom=fulltext