Scancell Share Discussion Threads

[supernumerary] 26/4/2023 12:08

Another cancer vaccine awaiting melanoma results:

[marcusl2] 26/4/2023 08:29

Bought some more.

Just to add that as we know iScib is suitable for ALL patients regardless of human leukocyte antigen (HLA) type. Scib is 40%.

That and electroporation deterred big pharma from licensing it.

Preclinical work suggests that clinical benefits (in terms of performance, efficacy, and ease of administration) of iSCIB1+ are a significant advance over SCIB1. Lindy said iScib cures 50%.

The addition of Avidimab has also extended the patent life.

Hopefully MHRA gives the nod for the change over to iScib soon.

[marcusl2] 26/4/2023 08:27

Burble

SCOPE TRIAL (SCIB-1)Today 06:16
I read an interesting thing yesterday. At AACR23, Moderna highlighted some of their advances in cancer treatment. In their P2 mRNA-4157-P201/KEYNOTE-942 ( ) trial which is investigating their patient-specific mRNA-based cancer vaccine in high-risk melanoma.

It was reported that, when combined with an immunotherapy, reduced the risk of disease recurrence or death by 44% in high-risk melanoma patients, compared to immunotherapy alone.

So whilst not a full trial read out from moderna, this gives us an idea of what others are doing in this area. We know that over 85% of patients were still alive 5 years after SCIB1 treatment and that was without an immunotherapy in conjunction with it.

Even more importantly to highlight, the Moderna vaccine is patient specific, with each vaccine dose requiring taking 34 antigen targets unique to a patient, manufacturing them as an mRNA vaccine before delivery. SCIB-1 is off the shelf. SCIB-1+ even more so as the changes Lindy and team have made mean this second version is suitable for a broader range of patients than the original.

I’ll be intrigued to see what results from our SCOPE study look like in comparison. Especially if we have managed to replicate the phase 1 results that we have seen previously.

Bermudashorts


RE: SCOPE TRIAL (SCIB-1)Today 08:02
Burble,

One of your links seems to be behind a paywall so have posted a link below which has a good summary of the Moderna results.

There was a brief discussion about the Moderna vax on here during AACR and at the time I went back and did a comparison with the SCIB1 results. The results for both vaccines were actually very similar with 18 month RFS tracking at 79% for the Moderna/Keytruda combination and 80% for SCIB1. However, when it came to safety, a quarter of the Moderna patients experienced adverse events at grade 3 or above versus just 2 SCIB1 patients, but I believe both of those were put down to the electroporation device rather than SCIB1 itself.

So with the caveat that it was in very small numbers, SCIB1 as an off the shelf vaccine achieved broadly similar results in a safer, quicker and more cost effective way as a monotherapy to Moderna's personalised vaccine given as a combination with Keytruda. The whole Ichor/FDA debacle was very costly and you do wonder where Scancell would be now had that combination trial run by Keith Flaherty in the US gone ahead.

Looking forward to Scancell finally getting the iSCIB1+ trial up and running.



Burble

RE: SCOPE TRIAL (SCIB-1)Today 07:20
8 weeks for high-risk melanoma is why I keep banging on about the USP of SCIB-1 (and Modi-1 too) being off the shelf products. They’re cheaper to produce, no waiting around and in this example would get to work two months earlier than bespoke made therapies

[octopus100] 25/4/2023 11:17

Its a shame as since initial reports from Trish at McMillan and more muted response from the company - all seems to have gone a bit quiet.
Any idea on when the next release of information on the trials is due to happen?
A couple of more response similar to Trish's would have been amazing.
I guess these trials take a long time and the quick response by Trish on McM board gave hope of it working very quickly but that seems to have petered out.

[panama7] 24/4/2023 22:39

Looks like biontech want to get back to concentrating on Cancer, wonder if they will be looking at Scancell.............The pharmaceuticals have made a lot of money, but their mRNA vaccines have failed. The Robert Koch Institut have stopped updating their vaccine dashboard, after almost four months of totally flatlined uptake; one of the foremost mRNA promoters, Bill Gates, has called the jabs a disappointment and compared them unfavourably to masks, of all things; and BioNTech, facing a revenue decline of 70 per cent, have announced an impending return to mRNA-based cancer therapies – their original focus upon their founding in 2008, where they’ve never enjoyed particular success. Perhaps if the vaccinators had proceeded cautiously, limiting their promises and injecting only the most vulnerable on a strictly voluntary basis, they could’ve preserved some future for their doubtful products. Instead, they oversold and over-administered their snake oil, and two years later most people have decided they don’t like it very much.

[markingtime] 24/4/2023 22:19

I see another poster on Macmillan is a possible entrant into the Modi-1 trial. Metastatic Renal Cell Cancer in this case....which, I see, has a median survival of about 13 months.Would be interesting to get an update on numbers in each cohort.

[inanaco] 24/4/2023 17:30

. Overall, analysis of PD-L1 on CTCs is feasible and could be detected prior to and after frontline therapy. However, there is no evidence on whether PD-L1 expression on CTCs could predict the response to anti-PD-1/PD-L1 treatment. This review examines the challenges that need to be addressed to demonstrate the clinical validity of PD-L1 analysis in CTCs as a biomarker capable of predicting the response to immune checkpoint blockade.

[inanaco] 24/4/2023 16:56

Your suggesting a Use .... Bermuda

how ever we are not using it ... and why would we

I appreciate that ctdna won't last long in the blood stream, however same, applies its a snap shot of what is happening, because if the t cells are working you will constantly get a stream of Ctdna to evaluate

and this trial will identify if modi1 clears distant mets and prevents recurrence

i would also point out that scib1 has been through multiple trials and they still do not use it

indeed they are testing for Pd-1 by biopsy

""A biopsy sample of tumour available for analysis of programmed death-ligand 1 (PD-L1) expression.""

and AGL have a paper on melanoma






ATB

[bermudashorts] 24/4/2023 15:07

The half-life of ctDNA in the blood is between 15 minutes and 2 hours, so is actually shorter than CTCs.

As has been pointed out, ctDNA liquid biopsies simply analyse and measure fragments of dead tumour cells shed into the bloodstream. They can be used to assess tumour burden and response to treatment by measuring frequency and volume of shedding and also for analysis of genetic mutations. However their utility is limited by the fact that RNA analsysis is possible but very difficult and analysis of protein expression is not possible at all. Many cancer therapies target proteins such as HER-2 or PD-L1 for checkpoint inhibitors.

On the other hand, CTCs are live whole cells and can be fully interrogated for DNA, RNA and protein expression. They can also be cultured and 'grown' in the lab.

So CTC liquid biopsies will give you much more information, but ctDNA is cheaper and faster. Each has its place and both complement one another. As far as Scancell are concerned, as this is a phase I/IIa trial, it's likely that they are simply using ctDNA to try and track response to treatment. In future trials they may decide that CTC analysis to measure protein expression such as PD-L1 or even cit. vimentin and enolase expression will be useful.

[inanaco] 24/4/2023 14:10

we are not testing an active drug Mia ....

the activity comes from T cells not the vaccine and they only trace they leave is in the Ctdna



ATB

[miavoce] 24/4/2023 13:55

Hi inanaco - live CTC's have been obtained from human blood 4 days after the sample was taken so they have much longer survival capability than 1 - 2.4 hours. I guess once they are out of the circulatory system and the hazards it presents they can survive a lot longer.

The main point about using Parsortix in trials is that as cancer can change over time the use of CTC's allows the pharma's to track how the cancer is changing so that this can then be correlated with any changes in the effects of the drug being trialled.

[panama7] 24/4/2023 13:25

I imagine Big Pharma will be fighting over Covidity in the coming weeks with the new sub variant Arcturis running rampant. How many 100's of millions do you reckon it will be worth after all we know the current jabs don't stop transmission, don't stop you getting infected and don't prevent hospitalisations. Bearing in mind the 10's of billions spent so far Covidity has to be worth a few billion, can't believe the share price isn't exploding.

[inanaco] 24/4/2023 12:33

From that link i gave

circulating cells only survive 1 - 2.4 hrs

Parasortix is at best a snap shot unless you are using the cells for other purposes but in Scancells case we are not.

Scancell is looking for a snapshot of the damage done to the cancer by the vaccine
rather than looking at what they already know ...

so Parasortix is best looked at by the oncologist treating a "new patient" and that would be set against looking at a biopsy to establish from scancells point if the cancer is an "immune desert" or has inflammation from an existing immune response, this is the issue from our point of view we are looking at the immune system not the particular genetic make up of the cancer, because we already know what constitutes citrullination and homo citrullination which caused cells to become "circulating" and we are targeting that EMT ...



Despite all of this help, CTCs persist in circulation for only 1–2.4 h according to in vivo experimental modeling and data from a small cohort of five patients (Meng et al., 2004). Most CTCs die in circulation as a result of shear stress and/or anoikis (Labelle and Hynes, 2012; Vanharanta and Massagué, 2013). Paradoxically, the half‐life of CTC clusters in circulation has been reported to be shorter than that of single CTCs, but this may be because large clusters get ‘cleared’; from the bloodstream or get stuck in capillaries more often than single CTCs (Aceto et al., 2014). Theoretically, survival signaling due to cell–cell junction‐derived signaling, reduction in shear stress experienced by individual components of the cluster, and longer dwell time in tiny capillaries should promote viability of CTC clusters versus single CTCs.

[marcusl2] 24/4/2023 10:25

Thanks Mia.

I was just thinking about how it could be of benefit in the Modi-1 and Modi-2 trials.

[miavoce] 24/4/2023 10:15

Hi Marcus, as you say Parsortix is cleared for clinical use in MBC.

Parsortix can however be used for all cancer types in non clinical activities such as CTC capture in drug trials, CTC capture in Laboratory Developed Tests LDT's offered from CLIA approved labs) etc.

[marcusl2] 24/4/2023 09:56

Am I correct in thinking that Parsortix is only cleared by the FDA for metastatic breast cancer ?

[inanaco] 23/4/2023 22:47

anyway its a huge subject ............



but

In addition, many epithelial tumours, such as breast, ovarian, gastrointestinal and prostate switch from expression of cytokeratin to vimentin during metastasis in a process known as epithelial mesenchymal transition (EMT). This change in phenotype enables the cell to become mobile and metastasize to new locations in the body.

we have two Vimentin proteins on the case

The second target protein is the metalloenzyme alpha-enolase (α-enolase), which is involved in the process of glycolysis. Many tumours tend to favour metabolism via glycolysis even in normal oxygen conditions (the “Warburg effect”) and generate energy by converting pyruvate into lactate. The α-enolase enzyme mediates the penultimate step in this metabolic process and is overexpressed in a variety of cancers.

we have one enolase on the case ....


coming soon another arm to assist ..... Modi2

[inanaco] 23/4/2023 22:30

I understand what it does Mia .... but ctdna gives you what moditope is killing which is great news for us ... once the cancer has been eliminated we then need to know if we have taken out micro mets ... i appreciate parsortix may find no circulating live cells after treatment but it cant find those already seeded until they appear on scan and that is 6mm

and we already know that stem cancers cells come under the influence of Modi1

Maintenance of the pluripotent stem cell state is regulated by the post-translational modification of histones. The discovery that citrullination of the linker histone H1 is critical to this process represents a new role for the protein arginine deiminases (PADs) in development.




this is why i keep saying separate the vaccine from what is in trial

modi1 induces CD4 Killer T cell "proven"

do they work ? so far ... yes because that is what the trial is about now


ATB

[miavoce] 23/4/2023 17:55

Hi Inanaco

ctDNA only provides a partial view of the cancer i.e. analysis of DNA fragments from mostly dead cancer cells.

Angle's Parsortix enables live cancer cells (both epithelial and mesenchymal) and cells undergoing E->M transition, and cell clusters, to be obtained from patient blood. These live cancer cells can be used for:-

- DNA sequencing
- RNA sequencing
- Protein expression analysis
- Cell culture

By using live cancer cells a full picture of the cancer is available whereas ctDNA provides a very partial picture.

Pharma's are now starting to adopt CTC analysis in their clinical trials (Angle now have five Pharma customers, and others in the imminent pipeline). The analysis is repeated at multiple time points in the trial. IMO the analysis of CTC's will become a standard part of cancer drug trials in due course because of the richness of information that it can provide.

Having a complete analysis of the CTC's from patient blood could provide Scancell with valuable information, which they might otherwise not have, in relation to why some patients are responding and others are not.

[inanaco] 23/4/2023 16:55

good news thou ... tickets for Division 1 are cheaper Loggie ...

[inanaco] 23/4/2023 16:53

Miavoice ....

You can try and bore me with the details ... ATB

as i am interested