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For immunobody, maybe the powerful effect of the dual presentation could not be achieved by anything other than a DNA plasmid.
Is to Potent what?
clever answer .. however i know exactly what lindy is thinking .. Immunobody is to potent
Inanaco,
I think I have only ever emailed Lindy Durrant twice and the first time was to ask exactly that. ie. the possibilities of creating an mRNA vaccine for Moditope. Her reply was that it was possible but that because Moditope exploits PTMs then peptide vaccines are much more effective.
Personalized neoepitope cancer vaccines
Sahin and colleagues have pioneered the use of individualized neoepitope mRNA cancer vaccines121. They use high-throughput sequencing to identify every unique somatic mutation of an individual patient’s tumour sample, termed the mutanome. This enables the rational design of neoepitope cancer vaccines in a patient-specific manner, and has the advantage of targeting non-self antigen specificities that should not be eliminated by central tolerance mechanisms. Proof of concept has been recently provided: Kreiter and colleagues found that a substantial portion of non-synonymous cancer mutations were immunogenic when delivered by mRNA and were mainly recognized by CD4+ T cells176. On the basis of these data, they generated a computational method to predict major histocompatibility complex (MHC) class II-restricted neoepitopes that can be used as vaccine immunogens. mRNA vaccines encoding such neoepitopes have controlled tumour growth in B16-F10 melanoma and CT26 colon cancer mouse models. In a recent clinical trial, Sahin and colleagues developed personalized neoepitope-based mRNA vaccines for 13 patients with metastatic melanoma, a cancer known for its high frequency of somatic mutations and thus neoepitopes. They immunized against ten neoepitopes per individual by injecting naked mRNA intranodally. CD4+ T cell responses were detected against the majority of the neoepitopes, and a low frequency of metastatic disease was observed after several months of follow-up68. Interestingly, similar results were also obtained in a study of analogous design that used synthetic peptides as immunogens rather than mRNA177. Together, these recent trials suggest the potential utility of the personalized vaccine methodology.
what i find intriguing ... Lindy and indeed trent .. have not even considered the RNA route .. for any cancer vaccine ... including
Moditope ..
good discovery ... wish they would indicate the cells in the VID and exactly what its doing .. a quick read gives little away
the science research paper titles don't mention DNA plasmids ... even thou RNA and DNA are similar .. both have to "go into" cells
Inanaco,
I don't know - I've just started looking at it as an area potentially worth investing in. It is possible because there are companies doing it from a simple blood draw. As we both have said, it might not be possible to take it to the level of home testing as I think they require a standard blood draw of 8ml and finger prick testing obviously won't do the job.
Anyway moving back to Scancell (sort of), I noticed that BioNTech/Pfizer are using a lipid nanoparticles for delivery of their COVID vaccine, link to company supplying them is below.
https://acuitastx.com/
10 to the 11 is 100 billion just in case algo appears
find a needle
Approximately 4 × 10 to the 11 T cells circulate in the adult human body ...
that is 100 billion ...
actually i had read that ... but did not see the "significance of the TB" rather i was looking at the Covid ..
but my thoughts are .... having a test that requires the "activation" of memory cells might not go down well in a pocket test ... health and safety issues
Inanaco,
I think you may have missed the :) in my post - an attempt at lightening the mood, tongue in cheek etc. etc.
i was playing catch up ...... you should consider that i actually went back 24 hrs to read your posts ................ then the thread took off from yesterdays post not today's .. not even looked at them yet ... !!
I always suspected you didn't read my posts beyond the first couple of sentences :)
Link is in my very first post this morning.
T B is a chronic condition ? so are you not looking for active T cells .. ?
do you have a link ?
The company I linked to is already producing a test. They've taken their approved TB T cell test and repurposed it for COVID 19 antigens, not sure whether they'll seek regulatory approval or not. So the technology exists at the moment but it doesn't look like there will be any sort of test that can be used out in the community that will quickly produce results.
Having said that, if more evidence builds on the Karolinska findings then the need for a T cell test is going to become greater and greater and some of the diagnostic companies will respond, in a similar way to the response we've seen on antibody testing. From an investment viewpoint, the trick is finding them and timing.
Either way, it's looking increasingly likely that if Governments, public health authorities want an accurate picture of immunity within populations, they're going to have to look at a combination of antibody and T cell testing. It's so interesting to see scientist's understanding of how this virus operates and how our immune systems respond evolve in front of our eyes.
Crumbs - thanks for that, I wondered whether someone had taken over .
this is what i was saying about the TCR patent...... you end up with Multiple T cells even against the same target which are different .. this is then the T cell repertoire ... but this could be 100,000 or higher ..
only a clone is the same as the original ....
so any test has to consider the repertoire of TCR to the target .... so then the test has to deal with that tolerance
but also the consequences of the infection ........... memory cell repertoire
vaccination ............ the issue is if you have antibodies then you will also have a t cells response it all depends which route the vaccine takes ... because the B cells (those cells that secrete antibodies) can act as APC .... they only need a CD4 helper to activate so that then generates a cognitive T cell response .. from the B cell
maybe its best to find a very highly sensitive antibody test .... but then you may get false positives ..
IMHO a simple T cell test is not likely ...
may well have Bermuda ... but who took up the patent .. ?
however if you watched that display of advertising and showboating yesterday ... and Dawn Butlers efforts to challenge the GOV Advisors .. on "language" .... OMG ..
Inanaco,
Yes thanks - had forgotten about ImmunID, I thought they had gone bust?
I was after someone who is developing a T Cell test to look specifically for COVID-19 antigen T Cells. Think I've found it here but looks like a long way from being a standardised test that can be scaled up for huge volume testing.
http://go.oxfordimmunotec.com/t-spot_discovery_SARS_CoV-2
this thread is directed at bermuda from his post to Ray ... only just seen it .
"" and therapeutic interactions including viral challenge,""
Active immune therapies have shown promise in treating cancer and result in durable
responses in some patients. However they can also produce severe side effects as immune
responses against normal tissue may be generated. There is thus a need for an effective
biomarker to identify those patients most likely to respond to these therapies.
Greater T cell diversity has been linked with improved anti-tumour responses. The TCR is
formed by the rearrangement of germline encoded sequences, and includes one variable (V)
and one joining (J) gene sequence. The large number of V and J genes available allows the
generation of a very large TCR repertoire. TCR diversity naturally declines with age and can
also be reduced by pathological and therapeutic interactions including viral challenge,
immunisation, and immunosuppression from chemotherapy or bone marrow transplants.
ImmunTraCkeR®-Melanoma uses patented Multi-N-plex® PCR technology to qualify and
quantify the relative amount of each different V-J combination and thus the diversity of the
TCR repertoire. In this way, ImmunTraCkeR®-Melanoma can assess the patient’s eligibility
for treatment (based on their immune status) prior to treatment with immune checkpoint
inhibitors. ImmunTraCkeR®-Melanoma may also:
? Establish a baseline immune profile to enable treatment to be tailored as patients
with different baseline immune profiles may respond differently.
? Monitor immune profile changes under treatment.
? Help identify patients unlikely to respond to immunotherapy, therefore avoiding the
use of expensive but ineffective treatments and their associated side effects.
can they tighten the parameters ... ?
I can see why that would interest you ..... in that the Gov track and test ... in fact the worlds system for track and test is probably missing the "infectious" that have a cd4/cd8 t cell response with a weak b cell response .. in which case its an open market. However its a serious amount of work to find those signature T cells ..indeed the scib1 test that panel .. could be adapted
ImmunID has been a pioneer in the field of immune molecular diagnostics for a decade. Its clinical product ImmunTraCkeR® evaluates a patient’s immune status, from a simple liquid biopsy (5ml EDTA blood), based on T lymphocyte repertoire diversity. ImmunID has developed and patented the ImmunTraCkeR® diagnostic assay and is expanding its clinical utility to become the general immune companion diagnostics for all immune therapies and especially immune checkpoint agents.
so basically it could be adapted to track the repertoire of cronovirus infections so you could get a background from previous indicating cross reactivity in people that have not been infected and the more specific of covid itself ...
extremely useful if you could predict disease progression from it ... ie identify cross reactivity as well