Member Info for RayPointer

The SP is battering away at that resistance level LOL.
I'd actually forgotten that 10 comes after 9. My brain thinks in binary.

I actually wouldn't include support/resistance levels as part of TA.
They actually work much better on large markets like the one my program runs on.
But even on small shares they can sometimes have an effect. 10p was once a strong support level for Scancell.
I agree that TA is mainly hocus pocus.

However, put yourself in the mindset of a trader who has an eye on Scancell. The administrators of CF selling a huge number of SCLP shares (huge in the context of a small AIM share); possible buying opportunity he thinks. He sees other people buying so he takes the plunge. But then when to sell? He could just maintain a trailing stop or he could look back in the charts for a spike or both.

Well resistance levels are there to be broken.

Agreed rats.
I also think we are at a resistance level (look at the 6 month chart and Jan 22). This is the kind of spike that traders look for IMO.

"You and I both know whats happening here..."

What is happening Knowlesi?
I'm just curious

"Nice to see glycan MABs make much more of an appearance"

Yes, crumbs and "ready to license" is repeated from previous presentations.
My theory is that it is not one of the central pillars of Scancell's grand plan.
I'm guessing here but it may be that Scancell are progressing the patents and looking for a pre-clinical deal.
Of course,I may be wrong.

Yes, at this crucial period for Scancell, it is nice to have frequent updates from the BOD.
Let's hope CH is successful in getting a copy of the recording.
Thanks for asking Chelsea. If you don't ask you don't get.

"Scancells ‘slow and steady’ progress certainly lowers the risks of ‘stalls’ along the way in my opinion !"

I would agree with that. Scancell want to maximise their chances of successful trials especially with their lack of cash.
It's all right for the Kites and Junos of this world (prior to being bought out) who raise much larger amounts of cash so they can afford to run more trials.
Martin Diggle did comment on the disparity of funding between US small bios and those in Europe.

"ZEJULA works to slow the return or progression of cancer
ZEJULA is a PARP inhibitor, which means it can help prevent cancer cells from repairing their damaged DNA. This may slow the return or the progression of cancer. ZEJULA can also affect other cells and tissues in the body."

https://www.zejula.com/en/patient-efficacy

It will certainly be interesting to compare Modi1 to zejula.
Zejula is an inhibitor aimed at slowing progression or return of the cancer. So, like CIs, it is defensive in nature, and presumably gives the immune system a better chance to attack the cancer. The aim is to stop damaged cancer cells being repaired.
Now Modi1 is an attacker with the aim of destroying tumours. A very different approach and, if it works, is likely to be more effective IMO, hopefully much more effective.
Lindy has never gone for the defensive approach and reckons that Modi1 will not require help from an inhibitor.

So what does Modi1 need help from? Well Lindy says it may need help from Modi2. If citrullination is low for a particular patient, Modi2 gives you an extra chance by targeting homocitrullination. She says this in her presentation at the last AGM. In fact she also says she is very excited at the prospect of combining the 2 vaccines.

The Tick, Tock to the Modi1 trial starting is only of the order of 6 months away and this includes ovarian cancer in phase 1
Interesting times ....

If Lindy can see an improvement that she thinks needs to be made, she goes ahead and makes it.

So we see in Moditope's case she saw that the addition of amplivant to the 3 targets in the vaccine would make a marked improvement. From memory the improvement was from 70% to 100% in the survival of mice.
Now this particular improvement must have proved to be tricky since the delay was of the order of 18 months (again from memory).

I'm making a guess here but maybe the difficulty was joining amplivant with the 3 targets in the most effective way i.e where is the best place to join the 2 molecular structures to achieve maximum improvement.

https://www.isa-pharma.com/technology/amplivant-technology/

"ISA’s AMPLIVANT® technology comprises a proprietary and synthetic Toll-Like Receptor (TLR)1/2 ligand with enhanced immunostimulatory activity that can be coupled to the peptide in the standard SLP® manufacturing process. Long peptide-AMPLIVANT® conjugate immunotherapeutics allow lower dosing at higher efficacy through better dendritic cell antigen processing and presentation as well as enhanced T cell priming."

So amplivant provides
1) Lower dosing
2) higher efficacy through better dendritic cell antigen processing and presentation
3) enhanced T cell priming (activation)

This last effect is the one that most interests me - Enhanced T Cell priming
Maybe it is this that gives the extra boost to Moditope and is the real cause for the increase in survival.

Initially I thought that TCell activation was binary - i.e. it was either activated or not. However Lindy states that when the Moditope activated TCells interact with the tumour cell they become further activated. This kind of supports a level of activation rather than a binary state.

So, going back to activation of the TCells by the APC - does amplivant give a higher level of activation to an individual TCell compared to that achieved without amplivant present?

Yes, you couldn't have written a better script

I'm more worried about the paint!

Must be very exciting paint Rats

Yes, it looks complex.
One point that stood out for me was that Antibody-Antigen binding is easier to understand than TCell binding. There's obviously a lot of research going on in this area as the binding mechanisms are not clear-cut to say the least.
Low affinity of TCR binding does not necessarily mean low avidity for instance.
I also noticed the phrase "optimal dwell time" which kind of suggests that the TCR needs to bind for a time that can be too short but can also be too long.

Thanks Inan
So CAR-T is designed to target antigens that do not exist as targets on natural T Cell Receptors.
So another difference.

Nom
We are talking about a science here that I only started to understand 18 months ago. So yes, I am glad of help to increase the level of my understanding.

So I've managed to persuade myself with your invaluable help that CAR-T and moditope targets are unlikely to work together.

It also looks like it may be difficult to create a memory effect with CAR-T therapy

https://www.ncbi.nlm.nih.gov/pubmed/31009109

So different receptors and also different mechanism of attack

This is a good discussion.
It may be something to do with how natural TCell receptors bind to the target as compared to Car-T engineered TCells.

https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell

"After CAR-T cells are infused into a patient, they act as a "living drug" against cancer cells.[3] When they come in contact with their targeted antigen on a cell, CAR-T cells bind to it and become activated, then proceed to proliferate and become cytotoxic.[4] CAR-T cells destroy cells through several mechanisms, including extensive stimulated cell proliferation, increasing the degree to which they are toxic to other living cells (cytotoxicity) and by causing the increased secretion of factors that can affect other cells such as cytokines, interleukins and growth factors.[5]"

It sounds like a very different mechanism to the natural TCRs that moditope uses which I believe are already cytotoxic and activated when they bind to the cancer target. Although Scancell do say they actually become more activated when they bind to the tumour.

Hi Wild

Thanks for your input.

It's probably me not quite understanding the science of CAR-T in this case.
My understanding is that CAR-T modifies TCells by creating extra receptors that are different to natural receptors.
Can they not be engineered to target the citrullinated epitopes that Modi1 targets?

So we know Modi1 has extremely promising targets and most likely the right delivery in CD4+ NK cells with natural receptors.
But can we exclude say the same CD4 NK cells (or even a different type of TCell) with the extra engineered receptors targeting the same citrullinated epitopes?

I believe the scenario is unlikely but what I am getting at is that CAR-T engineered receptors may possibly be superior to the natural receptors.

Yes, I understand that in CAR-T the receptors are engineered rather than being natural receptors.
But I think the hope with CAR-T is that the engineered receptors could perform better than natural receptors.
I agree that Moditope either by the vaccine or by TCR should do the job.