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[inanaco] 05/3/2023 10:03

Reovirus replicates in and eventually kills Ras-activated tumour cells, and as cell death occurs, progeny virus particles are then free to infect surrounding cancer cells. This cycle of infection, replication and cell death is believed to be repeated until all tumour cells carrying an activated Ras pathway are destroyed


RAS mutation frequency and hotspots in human cancers

RAS mutations occur in approximately 19% of all cancers, occupying a prominent role in tumorigenesis and tumor progression [3]. Among which, KRAS is the most frequently mutated isoform, followed by NRAS, and HRAS. RAS isoform mutations show selectivity in various human cancers (Fig. 2A). For example, KRAS mutations often occur in pancreatic duct adenocarcinoma (PDAC), lung adenocarcinoma (LUAC), and colon and rectal adenocarcinoma (with mutation frequencies of 66.1%, 16.5%, 30.3%, and 34.4%, respectively; COSMIC v94), whereas in hematological malignancies such as chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML), NRAS mutation frequencies are relatively high at up to 13.1% and 13.6% (COSMIC v94), respectively, reflecting the rates in malignant melanoma, thyroid carcinoma, and larynx carcinoma, which have NRAS mutation frequencies of 18.6%, 8.1%, and 9.7%, respectively (COSMIC v94). Although HRAS mutations are negligible in human cancers, salivary gland carcinoma, mouth carcinoma, and vulva carcinoma possess relatively high rates of HRAS mutation.

[inanaco] 05/3/2023 09:04

Supernumerary

transgene
The engineered virus used to carry the plasmids for the vaccine to transfect cells are in them self immunogenetic however they are discarded as they don't replicate once they have transfected the cell information into the innate and adaptive system, you should then end up with the T cells to the correct target ... get them potent enough and they can have a go at the cancer etc etc ... then down to the TME

but here is the big difference

you are introducing a replicating virus which t cells will activate against leaving you with a one Hit product ... because once you have immunity your introduced virus would need to adapt to try again from my understanding. so the actual inflammatory response is the t cells against the virus and virus infected cells and as with most viral infections they end up with a win for the t cells ... maybe that is why the initial data looks interesting but long term data doesn't, which is why the trial with PD1 produced the results that it did ...

when used with chemo you are exploiting the fast division cells being killed by the chemo and cells infected by virus, killed with t cells again same rules apply many treatments can only be done once, as the cancer builds resistance

so Transgene have something potentially called clonal expansion of the t cell population against the cancer and possibly supported by check point which could be ongoing over years

the t cells you have generated are targeting the virus and possibly being assisted by the check point to kill them faster as the t cells would have been suppressed by the cancer are now protected by the checkpoint clearing the infection faster

so this link is vaccinating against the reovirus ...

but an infection would have the same effect but maybe a few days behind as immunity built



Results Reovirus administration did not induce tumor-specific T cells but rather induced high frequencies of reovirus-specific CD8+ T cells directed to the immunodominant epitope. Priming of reovirus-specific T cells required a low-frequent population of cross-presenting dendritic cells which was absent in Batf3-/- mice. While intratumoral and intravenous reovirus administration induced equal systemic frequencies of reovirus-specific T cells, reovirus-specific T cells were highly enriched in the TME exclusively after intratumoral administration. Here, they displayed characteristics of potent effector cells with high expression of KLRG1, suggesting they may be responsive against local reovirus-infected cells. To exploit these reovirus-specific T cells as anticancer effector cells, we designed an SLP-based vaccination strategy to induce a strong T-cell response before virotherapy. These high frequencies of circulating reovirus-specific T cells were reactivated on intratumoral reovirus administration and significantly delayed tumor growth


Conclusions These findings provide proof of concept that OV-specific T cells, despite not being tumor-specific, can be exploited as potent effector cells for anticancer treatment when primed before virotherapy. This is an attractive strategy for low-immunogenic tumors lacking tumor-specific T cells.



so sadly i won't be investing and i am out

[bermudashorts] 04/3/2023 19:30

Super,

I beleive pancreatic cancer is the target for SC129, the mAb licensed to Genmab.

I think you've mentioned Oncolytics before. I see that pelareorep is being given in combination with an anti PD-1 and chemo and as you've highlighted, the results to date are really excellent. What's interesting is that the previous trial which was in combination with just Keytruda was discontinued as it failed to meet the criteria to progress to the next stage. Just goes to show the trial design is so important and even disappointing results can be extremely valuable in the design of future trials.

[supernumerary] 04/3/2023 18:29

inan - I was referring to serratia's post about use of an expensive engineered virus, nothing directly to do with Scancell or its candidates. I can't see Scancell going for panc - they're nowhere at the moment, and don't have the resources to take it through to registration themselves.

[inanaco] 04/3/2023 16:58

Supernumerary

we are not treating Pancreatic Cancer yet ... that's possibly Modi2

so the data you have presented compared to scancell Modi1, which his post eluded to, bears no resemblance to your post

ATB

[torquayfan] 04/3/2023 15:29

Inan - sorry I don't get that. But generally, as it is the weekend, why not give Sunak a chance? I'm NOT a Fan as you say, but at least it's good to have an Adult around.

I think most of us notice Boris the bold - BUT - he is so devious and dishonest and to see him squirming around now is awful, I cannot quite believe it. Until that is, I hear his 'Nadine' in defence . . . now he's surely finished ?

Which reminds me aptly - Saw Chuck at St Austell Coliseum 1980 and he was in the seat behind me - Brymon - Newquay - LHR the next morning - but that's another story.

And the words I remember were - 'Nadine, Honey is that true? ' - in which case - NO chance.

All good fun - off to Kanchanaburi 2m. ATB

[inanaco] 04/3/2023 15:02

me or the telegraph ? Tf

[panama7] 04/3/2023 14:54

TF, carry on living in denial as the Truth is being exposed. It's what order followers and cowards do.

[torquayfan] 04/3/2023 14:07

P7 - BFN again

If you diggers would stop baiting Inan - it'd be better here and there.

[panama7] 04/3/2023 13:36

They have not remotely been prosecuted. they committed Crimes Against Humanity and Treason against the people and fully supported by Labour and the Bill Goats funded MSM and MHRA.

[inanaco] 04/3/2023 10:24

and lets be fair to the police ......... they got manipulated by the Gov

but it backfired on the Government

as they got prosecuted ....

including Rishi

[inanaco] 04/3/2023 10:14

what ever the Government of the day agreed on Covid ... Labour wanted more

and that is the problem .....

the entire establishment was in agreement with how the pandemic was presented to the public

the question then is Should Gov be run from Whats App ..

[inanaco] 04/3/2023 10:08

P7

please go back through my history .... you will find posts

"protect the 20%" leave the rest to generate herd immunity

why do you think only you have it correct ?

i also posted stopping flying is crazy and i did not agree with Masks because folks don't know how to use them and most will not be surgical

some how you have taken the view that we all wanted to close the country that is not the case

[panama7] 04/3/2023 10:03

Inane, MT. EE, Ruck, Bermuda, Miavoce, TF et al, the damn is breaking , the truth is being exposed,. When are you Covid Zealots going to admit the truth and apologise to all those you demonised and vilified or does the Jab prevent you from doing so. I really feel sorry for your families having to live with truth deniers and enemies of Humanity.

[markingtime] 04/3/2023 09:58

Cuckoos always push everything else out from whatever nest they take over, sadly, DC.It is disappointing that they would rather focus on eliminating everything else instead of sticking to the topic. I posed a question some while back - only Marcus had a stab at it. No doubt the car park attendant was "busy"....lol

[inanaco] 04/3/2023 09:36

you have Ruck now implying that comments made in the past by the new Chairman some how relate to Scancell .......

who will challenge it ... LOL


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RE: SCLP Marketing DivisionToday 08:42
Cleaner,
Yes, very interesting and pertinent to Scancell.
Reminds me of the capability maturity model. I'd thought that Scancell were pretty immature but that was based on their journey towards providing a financial return. However, the nature of the business dictates that strict processes and controls are in place.

Interesting comment from J-M
"We had a tendency to develop products because we could do it and not because they were wanted in the market,”
So possibly concentrate on The Moditope platform and sell the rest off?
Then look for better commercial opportunities elsewhere?

[dominiccummings] 04/3/2023 09:25

OK inanaco won't stop trashing this thread, won't stick to his original thread, how about everyone else stops posting here so he has no one to 'play' with?

[markingtime] 04/3/2023 08:51

It does. Marcus is right.

[inanaco] 04/3/2023 08:46

says it all

[markingtime] 04/3/2023 08:40

Hey ho. Get a life, car patk boy....heh heh