Member Info for RayPointer

As I understand it, it is sometimes the market maker who is at the opposite end of a trade.

So, for instance if you are selling, there may not be a buyer at that time. So the MM will buy and the seller may not get as good a price as when buyers are around.
The MM takes the risk that he will be able to offload the stock at a profit OR he may refuse the transaction.

One of the functions of the MM is to create liquidity.

Thanks Inan.
It's nice to know that Lindy appears to know of at least one other group with a similar approach.
The high avidity of the Tcells looks to be the aspect that gives Scancell a distinct advantage over other groups.

It also looks like it may be the TCells targeting the receptor biding domain of the spike protein that stimulate the production of the neutralising antibodies. Do you agree Inan?
If this is the case, I would imagine that the high avidity TCells should produce a better antibody response when compared to Tcells with normal avidity.

This is quite interesting

https://www.abcam.com/protocols/the-immune-system-and-the-antibody-response

"An antibody response is the culmination of a series of interactions between macrophages, T lymphocytes and B lymphocytes. Infectious agent antigens are engulfed and partially degraded by antigen-presenting cells (APCs), such as macrophages, Langerhans cells, dendritic cells, lymph nodes and monocytes."

Sounds complex, doesn't it.

"Lindy should find devising a coronavitus vaccine a piece of cake after finding intelligent life in Keele."

I'm not so sure Rats. I have always thought that the Potteries could quite easily be a Primordial Swamp.

As I understand it Lindy's approach has 3 targets

1) The N-protein that she thinks may be a constant
2) The S-protein that is a variable for different coronaviruses
3) The neutralising Antibodies that are attempting to block part of the S spike that is instrumental in gaining access to the bodies cells

Do we know if 3) is constant or variable over coronavirues?
Just a thought as to how effective Lindy's approach is likely to be in future coronaviruses and how easy it would be to change it.
It is likely just a case of changing the S protein target or does the Antibody target also need changing.

Morning Wild

Yes, I think Lindy has already said that the N protein is a constant in all coronaviruses.

Thanks Bermuda

Again for anybody new to Scancell
https://www.scancell.co.uk/Data/Sites/1/media/docspres/presentation-to-lsx-world-congress-february-2020.pdf

Look at slide 9. This shows the results of Scancell's SCIB1 trial in melanoma for patients in the adjuvant setting.
You may notice that at 3 years none of the 16 patients had died and at 5 years only 2.
The results could possibly have been even better since dosing of SCIB1 had to be stopped when it was discovered that the remaining stock of the vaccine had degraded.

And remember that SCIB1 is an Immunobody product.

Excellent reply Ruck!

These are in stock

https://www.thepsychictree.co.uk/products/crystal-ball-100mm?gclid=EAIaIQobChMIhZTh4bXH6QIVDO7tCh0nuAM8EAQYASABEgJBjvD_BwE

Here's the pdf associated with the article that Bermuda posted

https://www.cell.com/cell/pdf/S0092-8674(20)30610-3.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867420306103%3Fshowall%3Dtrue

I intend to read it later but the evidence of the importance of CD4+/CD8+ tcells seems to be growing and getting more publicity.

Here's another article about the recent Moderna press release

https://www.statnews.com/2020/05/19/vaccine-experts-say-moderna-didnt-produce-data-critical-to-assessing-covid-19-vaccine/

I had to laugh at this paragraph

"Moderna was one of several drug companies that met with Trump. Each company that auditioned in front of the President so that he could give out $$$$$ to develop a vaccine. Each company’s gave their ideas on how long a vaccine would take, Trump didn’t like that. When Moderna CEO said what Trump wanted to hear (the end of this year or before) he gave them money. Proving that to manipulate Trump just lie and tell him what he wants to hear. I would hate to be Moderna when they have nothing but words on Dec 31. They will be added to the long list of Trump’s enemies."

WTP

The first article you posted was interesting

"Additionally, other studies demonstrated that inhibiting autophagy by chloroquine in combination with sorafenib in an in vitro model of glioblastoma 55 and in combination with temozolomide in melanoma patients augmented antitumor treatment efficacy 56. The inhibition of autophagy was also demonstrated to potentiate the response to radiotherapy in ovarian 57 and esophageal cancer 58. The efficacy of autophagy in favoring cell death has been demonstrated in many other cancer models, such as breast cancer, leukemia, prostate cancer, and myeloma 48,49. However, to date, clinical trials have not demonstrated that autophagy inhibition associated with anticancer therapy provided reliable therapeutic benefits to patients 59. Currently, protocols targeting autophagy induction instead of autophagy blockade are under intense investigation in oncology 28,50,60. Nevertheless, no drug currently licensed by any regulatory agency was developed for autophagy modulation, although several approved agents indeed modulate autophagy to some extent"

It seems there is a lot of research being done to try to inhibit autophagy in cancer cells. This is because it relieves stress and hence promotes cell survival. There are also references to autophagy induction as a possible cancer treatment.

Although dated in 2018, there is no mention of Lindy's research. These guys need to read more.

Its a shame our Sally didn't study at Oxford

That makes perfect sense WTP.
The way Lindy described autophagy, the precursor was stressed cancer cells. One of the reasons for stressed cancer cells is lack of nutrients.

Wow!

Yes,I think I understand.
But what happens to the virus cells that have not infected a cell yet but have been caught by a virus neutralizing antibody. I would imagine the virus cell, because it can no longer enter one of the bodies cells, will slowly die from lack of nutrients. The demolition of these cells is what I thought we were seeing in yesterday's video.

One of the videos posted yesterday shows dead virus cells being smashed to smithereens by the bodies recycling agents creating masses of virus cell fragments. I should imagine it would take some time for the body to fully expel such a large quantity of fragments. So while this process of expulsion is taking place, I would imagine the subject can still test positive for the virus.

I think I remember Jonathan Ball saying he was responsible for designing some of the inserts in the DNA plasmid.
So, am I right in saying these inserts are responsible for creating the neutralising antibodies via another function provided by DCs?

Yes, a good video.
It puts into context the approach adopted by Scancell

https://www.scancell.co.uk/covidity

"The key design features of Scancell’s SARS-Cov-2 vaccine include:
1) Identical plasmid backbone structure to ImmunoBody® SCIB1 already shown to be safe in humans
2) T cell epitopes from N and S proteins predicted to bind to both MHC class I (for the cytotoxic CD8 Tc cell response) and MHC class II (for the CD4 Th cell response);
3) Inclusion of trimeric RBD region of S protein to focus neutralising antibody response to block virus entry via the ACE2 receptor
4) Inclusion of motifs (e.g., GC rich regions) to ensure it is immunogenic and that it is taken up directly by dendritic cells."

So 1) and 2) are pure Immunobody as I see it. CD4/CD8 TCells doing their stuff on the S protein and the N protein.
The obvious aim is to kill the virus cell and it looks like they get 2 chances.

3) So, an insurance policy for cells that are not killed by the TCells. The antibody is aimed at binding to the part of the S protein that is used by the virus to gain entry to our cells.

4) Is to ensure good take up by Dendritic Cells.

I would like to know exactly how the neutralising antibodies are created.
Any ideas Inan?

Perhaps this article gives us a clue.

https://www.frontiersin.org/articles/10.3389/fimmu.2019.01529/full

This explains it much better than I could

https://www.scancell.co.uk/immunobody

What sets Immunobody apart from other vaccines that activate TCells is dual presentation. The vaccine is presented directly to the DC and also indirectly (cross presentation) via muscle cells.

The DC recognises this dual presentation by giving the TCells very high avidity, much higher than vaccine using a single presentation. Here avidity means the ability of the TCell to bind to its target.

Scancell have proved that using either one but not both of the presentations does not give high avidity TCells.
The other aspect of dual presentation is that the TCells are much more likely to go through a process called clonal expansion. This is basically TCells splitting a number of times producing a high number of identical TCells which inherit the high avidity. So you end up with an army of high avidity TCells able to bind to the target.

Some of these TCells differentiate into memory cells that are long living. It is these memory cells that have the ability to become effector TCells again if the target should appear.