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the adjuvant in Modi1 ........... prompts the T cell phenotype to change to pro Inflammatory .. which is why you need less of them to start a response

but this "Th1" phenotype is absolutely imperative .. because without that you cannot break the cancers immunosuppression

nature does it in very complex ways ....

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839096/

then you consider

Immunogenicity is the ability of a particular substance, such as an antigen or epitope, to provoke an immune response in the body of a human and other animal.

Cd4 get very angry on discovery of the Modified peptide and activate and differentiate into killers because the provocation of the peptide

maybe that is the best way to look at it

Ray
its not the binding .. its the "instruction set" in how the T cell is configured which generates the potency

Vaccine Adjuvant. Vaccine adjuvants are molecules or compounds that have intrinsic immunomodulatory properties and, when administered in conjunction with an antigen, effectively potentiate the host antigen-specific immune responses compared to responses raised when antigen is given alone.

Blast from the past ....... how is life treating you . ?

I think its about as far as we need to go ... unless Lindy App gives a lecture .. its highly complex, you would need to work in that "Space" to fully appreciate

Group R may comprise an antigen and more preferably group R.sup.4 in formula (2) comprises an antigen. The antigen may be coupled to the peptide, in particular to the K.sub.m (SEQ ID NO: 19) peptide part, either directly or via a spacer molecule: a linker. A "linker" in the context of the invention is understood to mean a low molecular weight moiety with at least two attachment points for moieties. In this respect, a divalent linker has two such attachment points and a multivalent linker has at least three such attachment points. Via one of these attachment points, the linker is attached to the peptide moiety of R, and each of the one or more remaining attachment points are/is attached to a antigen as defined above. These attachment points originate from functional groups in the precursor of the linker and allow at least one antigen to be attached to the adjuvant compound according to the invention. A linker preferably has a molecular weight of at most 800 Da. This is all conventional chemistry.

scancell has used the word Linker

good luck reading this one .....

http://patft.uspto.gov/netacgi/nph-Parser?d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=9314521.PN.&OS=PN/9314521&RS=PN/9314521

Applicants found that the compound according to the invention is able to induce an improved immune response by functionally stimulating TLR2 as compared to the known Pam3Cys-SK4 (SEQ ID NO: 11). Without wishing to be bound to the following theory, applicants believe that the higher stimulation level is achieved by exchanging the bridging --CH.sub.2-group in the N-terminal palmitoyl moiety of the known compound into a --NH-bridging group. The fatty chains of the compound fit in the defined pockets in the dimeric receptor and it is believed that by incorporating the bridging --NH-- group, a hydrogen bridge is created. This results in a tighter binding of the ligand to the receptor, which in turn is beneficial to achieve the desired adjuvant activity.

that is what i was doing .. trying to see if the bond is "chance" meeting rather than some sort of catalyst

Ray only way to dig deep is a patent search on amplivant ... i cant find how they link the peptide and that's a lot of work to read a patent

Don't think i have that quite right ray ... i think i have describe part of the links in amplivant not the link to the peptide ... which is probably on the same theory

We hypothesized that a hydrogen bond could be formed between the phenylalanine at position 312 of TLR1 and the lipid tail of Pam3CSK4 when a nitrogen atom would be introduced in one of the palmitic acid tails of Pam3CSK4. Indeed, we found that this improved agonist induced enhanced murine DC maturation [16]. We named this novel TLR2-L Amplivant® (AV).

Hi Ray the connecting point i believe is a single hydrogen and that connects to a nitrogen via shared electron

so that is the attraction point ... Quantum Chemistry

https://books.google.co.uk/books?id=a4JhVFaUOjgC&pg=PA276&lpg=PA276&dq=N1+h1+covalent+bond&source=bl&ots=aD8JyiV_Sz&sig=ACfU3U1s628OUXlY4RVWjXgjjBGzhcx3DA&hl=en&sa=X&ved=2ahUKEwi4xuKukLHnAhVQTxUIHQY1CbIQ6AEwAnoECAcQAQ#v=onepage&q=N1%20h1%20covalent%20bond&f=false

Ivy

""""It just seems strange to me that you would prove scaling up of individual elements and then presume they would all act independently when you combined them.""""

They are Not combined like sugar in your tea ...

Its a conjugate .... so its not the case that this expansion is not simply a hydrophobic peptide, its a peptide linked to Pam3CSK4
which is the adjuvant ...

final stage is linking all three conjugates to form modi1

IMHO

""""Peptides
The following synthetic long peptide sequences were applied in this study, either as free peptide or conjugated to Pam3CSK4 or AV. SLPOVA CTL: DEVSGLEQLESIINFEKLAAAAAK, SLPOVA Th: ISQAVHAAHAEINEAGR; SLPHPV: GQAEPDRAHYNIVTFCCKCDS. Peptides were synthesized and conjugated to AV as described previously [12]. """""

so basically this is the adjuvant

A synthetic triacylated lipopeptide, Pam3CSK4, consisting of a central cysteine residue bound to three palmitic acid chains and a 5 amino acid long peptide (-SK4), was shown to be a highly efficient agonist of TLR2 with a favorable solubility profile

that then is linked to the peptide to form the

Pam3CSK4 by covalently conjugating the ligand to synthetic long peptides (SLPs)

so Scancell called these "conjugates" of which two are successful one still have issues ..

so the vaccine has three elements ... each one a highly modified peptide

which is why its not Milk Tea leaves and sugar

amplivant ..........

The cell surface-expressed TLR2 can form a heterodimer with either TLR1, TLR6 or in humans also with TLR10. Binding of triacylated lipopeptides to TLR2/1 and binding of diacylated lipopeptides to TLR2/6 leads to pro-inflammatory cytokine release [1], while TLR2/10 heterodimers are thought to act as inhibitory receptors on human B cells and appear not to play a role in DCs [9]. A synthetic triacylated lipopeptide, Pam3CSK4, consisting of a central cysteine residue bound to three palmitic acid chains and a 5 amino acid long peptide (-SK4), was shown to be a highly efficient agonist of TLR2 with a favorable solubility profile [10, 11].

In previous studies, we exploited the activating properties of Pam3CSK4 by covalently conjugating the ligand to synthetic long peptides (SLPs) and studied the potential of such constructs as cancer vaccines [12,13,14]. Not only do Pam3CSK4-SLP conjugates mature APCs, they also have the potential to target conjugated antigens to TLR2-expressing APCs. This was exemplified by the strongly enhanced in vivo T cell priming by Pam3CSK4-SLP conjugates compared to a mixture of free Pam3CSK4 and SLP [14]. Interestingly, while the maturation of DCs by Pam3CSK4 binding was shown to be essential for efficient in vivo T cell priming, TLR2 itself is not the mediator in the uptake of the Pam3CSK4-SLP conjugates [12, 13]. Furthermore, we demonstrated the superiority of Pam3CSK4-SLP conjugates in the induction of antitumor immunity compared to a mixture of free Pam3CSK4 and SLP [14].

Jin et al. co-crystallized the human TLR2/1 heterodimer with Pam3CSK4 and thereby identified the residues of the receptor interacting with Pam3CSK4 [15]. We hypothesized that a hydrogen bond could be formed between the phenylalanine at position 312 of TLR1 and the lipid tail of Pam3CSK4 when a nitrogen atom would be introduced in one of the palmitic acid tails of Pam3CSK4. Indeed, we found that this improved agonist induced enhanced murine DC maturation [16]. We named this novel TLR2-L Amplivant® (AV).

Ivy

they don't scale up the coupled peptide .. that would be unbelievable difficult

they scale up each peptide then chemically link them to the adjuvant

so where have you got this information from ?

""""individual conjugates can be scaled up but how they interact with each other successfully as one “ product” and then scaled up."""

40 TCR ............................... Project Blue Print

Scancell Holdings Plc (LON:SCLP) said it had received “significant scientific endorsement” of its technology after it and a group of collaborators were shortlisted for major award.

It teamed up with BioNTech, Genentech and ISA Pharmaceuticals to form Project Blueprint for Cancer Research UK’s Grand Challenge.

READ: Scancell makes two experience hires as it gears up for the next development phase
The team outlined plans to eradicate established tumours with its unique vaccine, which had Scancell’s Modi-3 treatment at its heart.

Taking this to a next level is exactly what BioNtech has done with its new Car T trial by transferring the Car T into the patient and giving a vaccine at the same time !!

I still believe we are looking at a complete package for cancer being developed, with Modi1 trial blazing with BioNtech. while that trial proves up the technology Scancells research time builds modi2 and 3 in the background with 40 TCR viral vectors assembled for personalized attack

I really would not underestimate whats going on ...

Funding

4 collaborations now that could provide the financial support that is required for this movement into the trial phase

Diggles recently topped up at 5.2p so is clearly committed to Scancells Progress and its certainly not in his interest to dilute his own holdings by allowing a third party investment below 5.2p ... indeed BioNtech float has potentially made the initial investors a serious amount of money possibly allowing investment from Germany for those that see this as the next £billion dollar dominated stock .... may only need the signature of BioNtech on that collaboration agreement to go commercial to kick start the SP ..

and of course "Avidmab" could be the little darling .... and still work as a combination with moditope or immunobody because of the way it primes the immune system causing further stress on cancer with cytokines to attract Immunobody T cells to the tumour site or inflame causing expression of epitopes via citrulliantion or homocitrulline .. bringing in the big Gun .. Killer CD4

all in IMHO

ATB

Looking back again i don't think they can update the market any further with news other than to say ongoing .. because its repetition work once they have

1/ the correct T cell to work with, clearly Mab2811 appears to find them and expand them however that is IMHO so if anyone wants to get confirmation maybe email Scancell

2/ Cd4 ""TCR"" have been built into the viral vector and transferred to healthy t cells

TCR
? Project delayed due to requirement for Health and Safety Approval (HSE)
? Lenti-viral transduction of T cells now working in the lab
? 40 TCRs recognising citrullinated/homocitrullinated epitopes to screen

? Building internal expertise
in TCR identification
(BioNTech collaboration)

Now we all know dealing with the Authorities is time consuming .. HSE

but whats clear, why would scancell start screening 40 other TCR if the 3 in the option agreement are of no interest to BioNtech ??

assumptions based on evidence is far better than Guess work by traders IMHO

This is definitely a process of scale up issue with this single conjugate if you look at the AGM slides from last year this jumps of the page

Development batches of three Drug Substances completed
? To supply material for preclinical toxicity and stability studies
? Formulation and analytical work

"completed"

hope that gives relief to some that the technical challenges can be overcome

The People won, they have true democracy back

That was May 2019 .......... it takes at least one year to manufacture plus toxicology ....

"""Pre-clinical studies have demonstrated that administration of SCIB2 as a liposomal nanoparticle results in potent immune responses and prolonged survival. The nanoparticle technology utilises known lipid carriers that are optimised to deliver SCIB2 DNA to immune cells. The liposomal nanoparticles protect the DNA from degradation and facilitate efficient uptake, expression and T-cell activation against cancer cells. The nanoparticle delivery system provides an alternative approach to electroporation, which has been used to deliver other ImmunoBody agents to patients. Cancer Research UK are now planning a clinical trial to investigate the safety and efficacy of the SCIB2-nanoparticle complex in patients with solid tumours. """

it still could be in the clinic this year ... ATB