Scancell Share Discussion Threads

[inanaco] 07/2/2024 10:32

to keep it simple .... in the ovarian cancer human blood tests Lindy deleted the t regs

in the up coming Renal cancer double CPi cohort

Lindy is using yervoy so enhance Moditope Cd4 t cells by restricting its associated regulatory t cell

I think PD-1 will have limiting effect compared to yervoy which is why scancell work highlighted the fact that the CD4 t cell is less affected by Pd-1 however that is not to say that other effector t cells joining the fight are not assisted because PD-1 works superb on CD8 t cells

IMHO

[inanaco] 07/2/2024 10:23

Although CTLA-4 belongs to the family of inhibitory lymphocyte receptors, it does not appear to transmit inhibitory signals into effector T cells (4). Rather, CTLA-4 may control key functions of regulatory T cells (Tregs) and of antigen-presenting cells (5–7). More recently, studies in mice revealed that the antitumor activity of CTLA-4 blockade is mediated by Fc gamma receptor (FcγRIV)-expressing macrophages in the tumor microenvironment (TME) via in trans depletion of tumor-infiltrating Tregs (8–10). We speculated that a similar mechanism might operate in melanoma patients, who show a response to ipilimumab.

results

Effective tumor control may be achieved by shifting the balance from immune tolerance to protective immune responses that eliminate cancer cells. Compared with baseline, only responding patients have decreased levels of intratumoral Tregs in postipilimumab tumor lesions, and, in addition, they display the highest CD68+/CD163+ macrophage ratio, indicative of a TME enriched with inflammatory macrophages. CD163 is a scavenger receptor for the hemoglobin–haptoglobin complex and is typically expressed by immune-suppressive macrophages (known as M2-like) (25), which have been associated with poor prognosis in patients with early-stage melanoma (26). CD163+ macrophages are known for secreting immune-suppressive mediators such as IL-10 and TGF-β, low tumoricidal activity, and promotion of tissue remodeling and angiogenesis (27). On the contrary, CD68+CD16+ are classically activated, M1-like macrophages that secrete inflammatory mediators such as IL-12, TNF-α, and inducible nitric oxide synthase; exhibit antitumor activity; and elicit tumor tissue disruption (28). Interestingly, both CD68+ and CD163+ macrophages from our patients express CD16 (FcγRIIIA; Fig. 3C). The higher baseline CD68+/CD163+ ratio and density of CD16+CD68+, as opposed to CD16+CD163+ cells in the melanoma lesions from responding patients, may reflect an immune-inflammatory TME enriched with a beneficial macrophage population.

[marcusl2] 07/2/2024 10:12

encouraging early results as a potential off-the-shelf treatment for patients with pancreatic or colorectal cancer, according to a study co-led by researchers at Memorial Sloan Kettering Cancer Center (MSK).

“Having a vaccine that’s ‘off-the-shelf’ would make it easier, faster, and less expensive to treat a larger number of patients,”

[inanaco] 07/2/2024 10:01

If you look at the preclinical data with Modi1 in ovarian to test human response in blood work Lindy deleted "T REGS" these are regulatory CD4 t cells that can control a response against a specific epitope because they are deleted in the blood test a full response by modi1 is observed in blood work so that you can assess response rate to the vaccine

what they wanted too know will the majority of patients respond or see that vaccine



you will see in that paper CTLA-4

this is the target for Yervoy

so they are not deleting the T regs but controlling

and from that article you can see just how important T regs are

and in cancer your own T regs can protect it ....

[inanaco] 07/2/2024 09:42

the important consideration is Moditope

if you look at all the results from that UV1 trial ... the biggest impact on the cd4 t cells comes from

ipilimumab (Yervoy®

if you scroll back a few years you will find my posts on this that indicated in research that effect

[marcusl2] 07/2/2024 09:27

On this occasion we have to thank Cleanerworld on LSE ;-)

[inanaco] 07/2/2024 09:27

all about timing now can we get another big block of shares into ISA in April ....

hate to put them in at £8 a share ...

LOL

with a 6k limit on capital gains .....

[sci102] 07/2/2024 09:12

Great detective work marcus! So we should have an update by then since they are presenting it.

[inanaco] 07/2/2024 09:08

well we will soon know in March

[marcusl2] 07/2/2024 09:02

I think it is actually at 16m20s

[marcusl2] 07/2/2024 08:57

Cleanerworld

Prof Sarah Danson author on the Scope trial poster and lead investigatoron modi trial in Sheffield , speaker at melanoma conference 2024Today 08:48
Melanoma Patient Conference 2024

Thursday 29th February – Friday 1st March, 2024

Location: Voco St Johns Hotel, Solihull, Birmingham, B91 1AT



09:25am - 10:55am SESSION ONE: Updates in Melanoma Medicine

Chair: Imogen Cheese

09:25am - 09:55am Clinical Trials Update. Innovation and Progress (Professor Sarah Danson)

The clinical trails update is important and will be interesting, because

Prof Sarah Danson , was listed as an author on the poster presented in November 2023 SCOPE trial to be presented at the 38th Annual Meeting of the Society for Immunotherapy of Cancer



Poster presentation title A DNA plasmid melanoma cancer vaccine, SCIB1, combined with nivolumab

+ ipilimumab in patients with advanced unresectable melanoma: Efficacy and

safety results from the open-label Phase 2 SCOPE trial

Authors Heather Shaw, Poulam Patel, Miranda Payne, Satish Kumar, Sarah Danson,

Martin Highley, Clare Barlow, Robert Miller, Fayaz Master and Lindy Durrant

Abstract number 1533

Session date and time Friday, Nov. 3, 2023, 9am – 7pm EDT

Location Exhibit Halls A and B1 – San Diego Convention Center

Also listed as investigator at the Modify tirial

Principal Investigator Prof Sarah Danson at

Cancer Clinical Trials Centre
Weston Park Cancer Centre
Whitham Road
Sheffield
S10 2SJ



Previously in 2022 you tube link from Sarah Danson



21 mins in Scope trial explained

[torquayfan] 06/2/2024 23:48

Hi Inan. Good to see all those posts and your undiminished conviction about Scancell! An interesting discussion on the LF thread too. ATB

[marcusl2] 06/2/2024 21:53

Novartis paying €2.7B for longtime antibody player Morphosys

[chilltime] 06/2/2024 19:29

Welcome 3nobody

Good to have someone on board that knows Ultimovacs well.

It’s good to have 2 companies attacking from the same angle as it helps remove doubt of a flash in the pan result.

In general over time it seems there was a view that peptide/DNA vaccines don’t work.

Mrna and personalised vaccines being the only way to go.

So for two in quick time to drop in good results would be fantastic.

I did read about one peptide type vaccine that achieved very little and went no further.



It’s not that peptide vaccines don’t work, those involved just didn’t have the tight answer.

So companies like Ultimovacs and Scancell have been sat in dark room ignored by the masses. Over the next few months both should be well under the spotlight of big pharma companies.

Obviously BMS have a head start as they are with both, which is down to the CPI combo being the standard of care.

Ulti have done Scancell a favour as 78 of those are just the CPI combo. Fresh data to compare against.

[marcusl2] 06/2/2024 15:29

Explained better at the AGM
From around 45m

[3nobody] 06/2/2024 14:37

marcus,

I have listened through the 30 Jan. presentation by Lindy. The Audio is a little bad and I have not found the part where Lindy think their vaccine is inferior to Ultimovacs. Could you possible narrow down where in the presentation this is discussed?

[inanaco] 06/2/2024 14:28

and a quote and deal

[inanaco] 06/2/2024 14:28

with Barclays

[nigelpm] 06/2/2024 14:27

None - I did a dummy purchase of 50k - quoted 11.78.

Consider another broker if you aren't getting quotes that often.

[inanaco] 06/2/2024 14:14

so how many did u buy

[supernumerary] 06/2/2024 14:07

Sci - thanks - I know you can trade pretty much anything on the derivatives platforms, but at the time I was looking at a multi-year hold, so I didn't think that CFD/SBs were really suitable.

[nigelpm] 06/2/2024 14:04

Plenty available just not below offer price.

[inanaco] 06/2/2024 13:58

had to do two £500 trades

[inanaco] 06/2/2024 13:38

still cant