Scancell Share Discussion Threads

[bermudashorts] 21/2/2019 12:32

Terror,

L&G have been selling. Scancell have recently updated major shareholders on their website. Previously they were showing holdings at July 2018 and a few days ago updated it to show holdings at 31st Jan 2019. Not much change in holdings other than L&G have reduced from 18,167000 to 16,300000 so a reduction of just under 2m shares.

L&G originally invested in 2017 with a 16m holding but increased in 2018 when I assume they took part in the placing (from memory in April). It may well be that they've sold down to their original core holding (or thereabouts) and are done for now and that's why Scancell have now updated their website. Let's hope so.

[terror] 21/2/2019 10:55

Lots of excitement on the MFF and shouts of 'something's going on'.

Bottom line is someone was selling and that appears to have stopped, allowing the share price to move up and retrace the losses.

Retrace to 10p and then 13.5p potentially. All depends on the nerves of some.

[oldnotwise] 21/2/2019 08:13

Thanks Bermuda, observations in your 19831 have increased my understanding of the last seven years substantially.
Not what I want to hear, but it makes a great deAL OF sense.
Good job we're not a one trick pony. :-)
ATB

[bermudashorts] 21/2/2019 07:57

TF - thanks for that.

Highlights just how far immunotherapy has come. When most of us invested in Scancell there were really no treatments for adjuvant melanoma - the field was empty and in a few short years physicians now have the choice of Yervoy, Opdivo and Keytruda.

So from a patient's point of view, real progress with new treatment options where there were previously none but still very expensive treatments with the potential for severe side effects. Disappointing that there isn't a safe, low cost and effective vaccine as an alternative choice!

SCIB1 was always intended to be an adjuvant therapy and it's such a shame that for the moment it's not being taken down that road. By their very nature trials in the adjuvant setting are long and require large patient numbers - the Keytruda & Opdivo trials had around 1000 patients each. Just beyond the reach of small bios.

[torquayfan] 21/2/2019 00:36

''Keytruda gets okay from FDA for adjuvant melanoma - February 20, 2019

The US FDA has approved Merck & Co’s Keytruda as an adjuvant treatment for patients with melanoma who have had surgery but still show some evidence of cancer in their lymph nodes.

It’s the first time that PD-1 inhibitor Keytruda (pembrolizumab) has been approved in the US for adjuvant use in any cancer, although Merck picked up European approval for this indication in December.''

[inanaco] 18/2/2019 11:20

point is Immunobody plus Pd-1 can reset the microenvironment ... it's not just one action ..

[inanaco] 18/2/2019 11:19

CD4 .... differentiate once ...

once you are a Cytotoxic CD4 ... the PD-1 ligand has no effect ..

Cd8 get turned off ....

CD4 Helper effector cells ... get told to suppress ...

research Th1 and Th2


CD4+T cells along with CD8+T cells make up the majority of T-lymphocytes. CD4+T cells after being activated and differentiated into distinct effector subtypes play a major role in mediating immune response through the secretion of specific cytokines. The CD4+T cells carry out multiple functions, ranging from activation of the cells of the innate immune system, B-lymphocytes, cytotoxic T cells, as well as nonimmune cells, and also play critical role in the suppression of immune reaction. Continuing studies identified new subsets of CD4+ cells besides the classical T-helper 1 (Th1) and T-helper 2 (Th2) cells. These include T-helper 17 (Th17), follicular helper T cell (Tfh), induced T-regulatory cells (iTreg), and the regulatory type 1 cells (Tr1) as well as the potentially distinct T-helper 9 (Th9). The differentiation of the different lineages depends on the complex network of specific cytokine signaling and transcription factors followed by epigenetic modifications. This paper will be focusing on the cytokine milieu and lineage specific transcription factors required for the differential development of the antigen-activated CD4+T cells, and also will cover a brief overview of the development pathway of mature naïve CD4+T cells, and finally the effector functions of each subtype will be summarized.

[bermudashorts] 18/2/2019 11:13

OK thanks - will have a read tonight. For some reason I had in my mind that personalised vaccines and Moditope = CD4 and vaccines targeting tumour associated antigens like ImmunoBody = CD8.

Point is though whether Scancell see Moditope as a monotherapy or not, if you have giants like Jim Allison advocating CD4 vaccines, then it must surely add to the appeal of the platform.

[inanaco] 18/2/2019 11:08

this paper and the importance of the Gp100 epitopes for Immunobody that generate CD4 +

[inanaco] 18/2/2019 11:03

Bermuda

In this study we have shown that although T cell infiltration resulting from SCIB1 DNA vaccination demonstrates proliferation and cytokine release it was also associated with increased levels of PD-L1 expression in the tumor microenvironment. Several published studies also indicate that the PD-L1 level within the tumor environment can be elevated by infiltrating activated T cells secreting IFNγ [25, 26]. The expansion and function of infiltrating high avidity T cells induced by vaccination could be compromised within the tumor by upregulation of PD-1 and engagement with PD-L1 in the melanoma tumor microenvironment [26–28]. Upregulation of PD-L1 provides another obstacle in the path of vaccine induced anti-tumor T cells. Therefore, the combination of vaccines with blockade of PD-1/PD-L1 signaling may further benefit melanoma patients, especially for late stage disease.

[inanaco] 18/2/2019 10:57

Bermuda . CD4 can differentiate

CD4 +T cells are crucial in achieving a regulated effective immune response to pathogens. Naive CD4 +T cells are activated after interaction with antigen-MHC complex and differentiate into specific subtypes depending mainly on the cytokine milieu of the microenvironment.


want of a better word ... Shape changers ...

so if the signal is to Suppress .......... They can !

[bermudashorts] 18/2/2019 10:46

Inanaco,

I thought ImmunoBody generated primarily CD8 response and Moditope CD4 - will check but am sure that's how Scancell have presented the two vaccines in the past.

[inanaco] 18/2/2019 10:22

Tf you have to appreciate that a Immunobody CD4+T cell is very important as not only its activity is to promote inflammation ...But when subject to the pd-1 ligand it actually promotes T cell regulation .. causing the immune system to go into reverse !!


These results suggest that the PD-1/PD-L1 pathway plays a role in Treg induction and is associated with impaired adaptive immunity. In the tumor microenvironment, PD-1 expressed on Tregs accelerates CD4+ T cells differentiating into Foxp3+ Tregs under the circumstances of CD3 and TGF-β. Foxp3 is a critical transcription factor of Tregs, which suppress Th1 responses [94]. Foxp3+ Tregs is a highly immunosuppressive subset of CD4+ T cells that is critical in suppressing proliferation and cytokine production of other T cells, inhibiting tumor-specific immune responses and maintaining peripheral immune tolerance in cancer patients [114]. Meanwhile, Treg cells express constitutive high levels of PD-1, which enhance Treg functional response or proliferation and inhibit T cells responses

this is another area that Can be blocked by Keytruda ...

which is why every bit of data i find tells me .. Keytruda Plus SCIB1 = Synergy

[torquayfan] 18/2/2019 10:01

Thanks Guys.

[inanaco] 18/2/2019 09:49

scib2 targets

CD4+ T cell epitopes NY-ESO-1 87–111 and 119–143

SCIB1 targets Gp100

[inanaco] 18/2/2019 09:18

He is understanding the importance of all CD4 + ... Immunobody also targets CD4 +
Helper T cells to become effector cells .. its this priming again that is so important in the way the T cell performs against cancer

by the way they have another form of self destruction as the immune response subsides, loss of the antigen and the cytokine results in them self destructing ....

the Kidneys and the Liver are not involved ...

[bermudashorts] 18/2/2019 09:02

TF,

It's this sentence:-

'“I think there are ways around that, involving the development of CD4-TARGETED AGENTS, particularly using VACCINES''

Moditope = CD4

[torquayfan] 18/2/2019 08:28

I remember seeing BB comments that Modi will function without CI ?
What are you getting at ? Thanks.

[bermudashorts] 18/2/2019 08:15

TF - yes it is and it was a genuine and important question.

[torquayfan] 18/2/2019 08:11

Bermuda - I'm just glad to see THE man enthusing about vaccines.
I thought it was a very interesting link.

[bermudashorts] 18/2/2019 07:44

TF

Thanks for that - so are we now suggesting that Moditope will also be a combination therapy?

[10acious] 17/2/2019 16:37

Come on now, don't be shy, say what you mean!