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""What is doesn't do is prove that the activated CD4+ TCells will go on to attack cancer cells in the same way as proven in Mice experiements. """

interesting one that Ray .......... can you prove T cells once activated to a target with the correct binding ligand and signalling won't kill ...

identifying a target ... and finding a suitable antigen are not the same ...
most of these investments in this sector is finding the antigen ........... 100's of millions invested in the search for that "immunogenic antigen ""

so SCIB1 has its "gp100 and its "tpr2"

modi1 has its "vim1/2 and enolase "

Immatics already has a CD8 TCR in the clinic so its shown its "operator" platform is "functional"

but it still has to find targets ........ back to the "antigen" again

this is why Scancell is so valuable .. if our "moditope antigens" translate in the clinic to efficacy ... Scancell is in the premier league and i really mean that

so moving back to the Calgene deal .........

The new deal includes the largest upfront Immatics has received for any pact, as well as the highest potential value attached to each target — which shows the increasing appreciation for such targets, Singh added.

all based around "targets"

the Modiope TCR based only on the Modi1 vaccine has already more targets that the immatics deal and we have not even considered Hommocitrulline

and folks are concerned about the SP .............. why ?????

SCIB1 in the clinic
SCIB2 in manufacture
Modi1 getting closer to entering the clinic
TCR deals could be close
Glycans ... scancell has already told us they have interested parties

so moving back to the Calgene deal .........

The new deal includes the largest upfront Immatics has received for any pact, as well as the highest potential value attached to each target — which shows the increasing appreciation for such targets, Singh added.

all based around "targets"

the Modiope TCR based only on the Modi1 vaccine has already more targets that the immatics deal and we have not even considered Hommocitrulline

and folks are concerned about the SP .............. why ?????

SCIB1 in the clinic
SCIB2 in manufacture
Modi1 getting closer to entering the clinic
TCR deals could be close
Glycans ... scancell has already told us they have interested parties

i hope now you can see why my eyes light up when I found the problem area i was concerned with on the Moditope TCR has been resolved

and its quite simple .............. a Naive CD4 T cell given a Moditope TCR does ""NOT"" make a Moditope encoded cd4 Killer T cell

it requires changes in the T cell structure otherwise the T cell does not know what it is .....

so a Cd4 T cell must differentiate into something ..... which is a highly complex engagement between the "epitope" and the dendritic cell which the t cells binds to to receive the "differentiate instructions" and the target epitope ...

that is when you get the "moditope CD4 killer"

how they have done it is unknown but it appears the collaboration has achieved the ability to "pre activate" prior to giving the t cell the new "TCR"

now that deal to day just highlights what is at stake ............ so while you are worrying about being "locked in and underwater" consider this ....

Scancell continues to surprise .... cheer up

Immatics scores $75M upfront in TCR deal with Celgene, as interest in tech burgeons
Months after elevating chief scientist Harpreet Singh to the post of CEO, privately-held immuno-oncology company Immatics has enlisted Celgene in a deal capitalizing on the industry’s appetite for TCR therapies and their potential to target solid tumors — a limitation of existing cellular therapies.

The Celgene deal gives Immatics $75 million upfront for three programs and up to $505 million in milestone payments for each licensed product if Celgene exercises the option. If all goes well, Immatics stands to earn more than $1.5 billion, in addition to tiered royalties on net sales. Celgene $CELG, meanwhile, is in the process of being taken over by Bristol-Myers Squibb $BMY — which means the fate of the deal ultimately lies with Bristol-Myers.

The new deal includes the largest upfront Immatics has received for any pact, as well as the highest potential value attached to each target — which shows the increasing appreciation for such targets, Singh added.

Violindog I thought you topped up at about 5p ... does that not = paper profit

Its ok Ruck ........ Bermuda and myself did the heavy lifting of explaining it ....

you did not ...

if you had been up to speed you would have led the discussion ...

are you "important " today ... in that respect ?

maybe in two years .. you can lead the discussion

to understand the Importance of how varied the CD4 t cells are (generals of the immune system) .... think of your "EyE" and just how sensitive it is ... even T cells protect the eye from inflammation of the eye

An important factor in the establishment of ocular immune privilege is the dynamic down regulation of T helper 1 (Th1) immune responses that occurs in response to antigens delivered intraocularly; a phenomenon that has been termed anterior chamber-associated immune deviation (ACAID). ACAID is characterized by the generation of splenic regulatory cells that inhibit the expression of delayed-type hypersensitivity. Previous studies have shown that antigens introduced into the anterior chamber of the eye induce the generation of a CD4+ T-cell population that suppress the induction of Th1 immune responses and the appearance of a second population of CD8+ T regulatory cells that suppresses the expression of Th1 inflammatory responses (= efferent suppressor cells). Experiments described here characterized the function of the CD4+ ACAID suppressor cell population and its effect on the generation of CD8+ efferent suppressor cells that inhibit the expression of DTH in situ. Both in vivo and in vitro experiments demonstrated that CD4+ T cells are required for the generation of CD8+ efferent suppressor cells. CD4+ T cells do not require cell contact with CD8+ T cells; instead they produce soluble IL-10 that is sufficient for the generation of ACAID suppressor cells. Finally, the CD4+ afferent T suppressor cells are not natural killer T cells, but do express the CD25 cell surface marker.

so these T cells are protecting the eye from the immune system responding to the threat .... which is why this area within the cancer is not just about check points and vaccines

its about rewriting the immune response using the vaccine as a template ...

so scancell is looking for

every thing the eye does not want ...

A model of CD4 CTL differentiation. After T cell receptor stimulation, a small fraction of naïve CD4+ T cells express class I-restricted T cell-associated molecule (CRTAM). CRTAM+ CD4+ T cells have the potential to differentiate into CD4 CTLs, which gain cytotoxic activity after incubation with IL-2 (Th0 CTL). Under the cultivation in the skewed conditions for each Th subset, they differentiate into Th1- or Th2-like cells with cytotoxic function (Th1 CTL, Th2 CTL). On the other hand, the majority of CRTAM- CD4+ T cells can differentiate into various Th subsets based on environmental cytokines. Th1 polarized CD4+ T cells are known to show cytotoxic activity, and it has recently shown that intestinal regulatory T cells (Treg) can convert to cytotoxic CD4 intraepithelial lymphocytes.

if you look at the Picture of Fig 1 .... in this link you will see may cd4 t cell "differentiation"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321676/

so with the Moditope TCR extracted you have to transfer that into the correct T cell linage which has differentiated into a C4 T cell Th1 (inflammatory) and its adopted Cytotoxicity .........

so that statement is wow ! if you understand just how complex this is ....

We pre-activated and differentiate the CD4 T cells before we transduce them with the Moditope TCR.

its a side show at this stage ... in two years it becomes important ..

However .. Ichor have deals with many big boys to who have a vested interest ...

But if you think """today""" its an Important Issue please explain ? .. only i am sure Scancell will not be looking for a deal without patient combo Data ...

also the value comes from patient data .......... it does not matter if they are American .... they are not a different race to us ...
That is what any deal done will be based on ... Patient Data .. signed off by a Uk Investigator or US only adds a different dimension ... but as all Pharma are Global in outlook ... and want to access all markets .. not just US or EU .. it makes little sense in worrying about Ichor at this stage. If Ichor have not got it sorted in 2 years then it could become a problem ... but is that problem then for Ichor or the FDA with multiple trials ongoing with Trigrid 1 and 2 in Europe and Korea already given the green light ?

We pre-activated and differentiate the CD4 T cells before we transduce them with the Moditope TCR.

that is the first bit of data ever on the subject

this is a side show compared to what i discovered earlier ..........

Bermuda and myself has explained what we think is going on from FDA process .....

master file ... Ichor submitted
IND which includes the use of ... Ichor by Scancell

questions raised to Scancell IND as regards the device have been sorted ....

Device specific questions from the master File are ongoing ..

they have to be ongoing otherwise scancell would have resubmitted straight away with a IND to include Clinical Trial centers in the US ... under a UK trial investigator

awaiting "clarification"

Scancell will resubmit the IND at a later date with the intent to initiate clinical sites in the US, following further clarification from the Agency regarding Ichor's TriGrid® 2.0 delivery device.

so the Ichor master file is NOT sitting on a shelf

why would it be back on the shelf ? (master file) it clearly has unresolved issues that are already under discussion .. FDA opened the file... and asked questions .. which are now not IND dependent .. otherwise Scancell would not have stated "device issues" I think your reading way to much into Red Tape Process ... when really none of us know ... as we are not involved

HOW FDA USES the CONTENT: FDA will only access your Device Master File when your customer makes a submission to the Agency and includes your access letter. Only at that time, as the FDA reviews the submission and as the customer designates within the submission, the FDA reviewer will open and review the referenced contents. This is when the customer will need to be specific as to how the content in the Master File supports their requirements for the submission

https://paladinmedical.com/device-master-file-fda/

Scancell IND was not approved, it cannot be approved until the package is approved, questions raised included Device /SCIB1 questions which got answered by Scancell and accepted as its now a Device issue not a vaccine issue but both have to be accepted before Full approval to start the trial ... so i suspect the master file from Ichor still sits with the FDA as this was submitted 4 weeks prior to the IND > so its not IND specific , but the Device and the vaccine is a package in the IND approval ...

the question is do you understand the significance of it ? Lindy did

i have posted the science i posted on earlier else where ... be interesting to see questions on that post that are challenging ...