Scancell Share Discussion Threads

[bermudashorts] 09/2/2019 13:15

Inanaco please stop telling lies.

[inanaco] 09/2/2019 12:14

But in all this ....

he has still failed to answer the fundamental question

which trial has failed

SCIB1 in Melanoma

or

PD-1 Keytruda in Melanoma ..

the reason why he cannot answer is because they have not Failed ....

so the Results of "Synergy" will be interesting as Bermuda's own Link to Pfizer Highlights

""""This has led to breakthroughs in the development of new drugs, and, subsequently, to opportunities to combine these with cancer vaccines and dramatically increase patient responses. Here we review this recent progress, highlighting key steps that are bringing the promise of therapeutic cancer vaccines within reach.""""

[inanaco] 09/2/2019 11:50

Bermuda ...Confirmation Bias

you tried it again in your post last night ... "" Based on your findings ""


"""" 2) Based on your findings are you predicting that 100% of patients in the SCIB1 combination trial will respond? If not why might they not respond? """

anyway at least i gave you reasons why SCIB1 will fail in patients which is why Scancell is not targeting 100% responders

[inanaco] 09/2/2019 11:30

This is a Classic case of

Confirmation bias, also called confirmatory bias or myside bias, is the tendency to search for, interpret, favor, and recall information in a way that confirms one's preexisting beliefs or hypotheses. It is a type of cognitive bias and a systematic error of inductive reasoning.


Scancell is Proven

so Boom is reading this as """ SCIB1 is proven with PD-1"""

when i am talking about the mechanism of action has been proven ...

scancells own Papers on synergy are proven ... the entire industry now seems to agree with that ...

except Bermuda .. who clearly read "scancell is proven" as "SCIB1 is proven"

this is not the case we are going around in circles ... !! Its a case you took the wrong turning from the start

[inanaco] 09/2/2019 11:05

Choice of words ... "Scancell is Proven" ..

LOL

Bermuda Scancell is not in trial ..

have a good day ...

SCLPwhy no comment ???27 Jan '19
INovio has Just proven Scancell ....................................................... if you reach my posts from 4 years ago you will find all the comparisons in the market between Inovio's HPV vaccine and the industry ...

it barely worked, something like a 10% differential between placebo and vaccine ...

yet here we are the same vaccine with a PD-1 plus il12 has two complete responders !!!

They used il12 as an adjuvant to get a better response from the vaccine ....

[bermudashorts] 09/2/2019 08:03

Inanaco,

With respect you don't get it because you're not listening to what I'm saying. You used the words 'Scancell is PROVEN' - not the PD-1 monotherapy mechanism of action is proven. Anti-PD1/L1 therapies are proven as they are approved treatments, they are also proven in combination with chemo and other CI's because they have been through clinical trials and approved. What is not yet PROVEN by any stretch of the imagination is SCIB1 or SCIB2 in combination with PD-1 - all you have is a mechanism of action and mice data which suggests efficacy but it is not PROVEN until it has been tested in clinical trials.

Regarding your quotation from Poulam Patel - the fact that 3 patients, (a mixture of resected and non-resected) were treated with PD-1 after they progressed with SCIB1 treatment is not PROOF!!!

Note the difference in language:-

Professor Poulam Patel - May, Suggests

Inanaco - proven

That's my issue and right at the beginning of this debate all you had to do was accept that was too strong wording for the stage Scancell are at. The raising of expectations too high in all sorts of areas really doesn't help Scancell at all.

This will be my last reply on the subject because we're just going round and round in circles.

[inanaco] 08/2/2019 23:36

So you wanted more proof ...




Anti-PD-1 therapy yields objective clinical responses in 30-40% of advanced melanoma patients. Since most patients do not respond, predictive biomarkers to guide treatment selection are needed. We hypothesize that MHC-I/II expression is required for tumour antigen presentation and may predict anti-PD-1 therapy response. In this study, across 60 melanoma cell lines, we find bimodal expression patterns of MHC-II, while MHC-I expression was ubiquitous. A unique subset of melanomas are capable of expressing MHC-II under basal or IFNγ-stimulated conditions. Using pathway analysis, we show that MHC-II(+) cell lines demonstrate signatures of 'PD-1 signalling', 'allograft rejection' and 'T-cell receptor signalling', among others. In two independent cohorts of anti-PD-1-treated melanoma patients, MHC-II positivity on tumour cells is associated with therapeutic response, progression-free and overall survival, as well as CD4(+) and CD8(+) tumour infiltrate. MHC-II(+) tumours can be identified by melanoma-specific immunohistochemistry using commercially available antibodies for HLA-DR to improve anti-PD-1 patient selection.

Scancells own results ......


Most tumors do not express MHC-II; however, 62% of the tumors in this study showed strong MHC-II expression prior to vaccination. MHC-II expression on melanomas has previously been described as an indicator of poor prognosis.30-32 However, in this study 9/13 of the patients whose tumors expressed MHC-II are either disease-free or their tumors regressed after SCIB1 treatment. This suggests that MHC-II expression could be a predictive biomarker of patients who are likely to respond to immunization. A recent study has shown that MHC-II positivity on tumors cells predicted response to anti-PD-1/PD-L1 therapy.(((33))) It also provides support for the growing evidence that tumor-specific CD4T cells play a vital role in anti-tumor immunity.34-37

(((33)))) is the link i have highlighted above

[inanaco] 08/2/2019 23:21

You mentioned an area of patients that might not benefit from Pd-1 or SCIB1

this is actually from tumor samples ...

Six patients had tumors that had lost expression of MHC-I (≤80% of tumor cells) and had no elevated expression of MHC-II (>15% of tumor cells). Only one of these patients remains disease free. Clinical benefit was superior in MHC-I/II positive patients (Fishers exact test p = 0.027).

[inanaco] 08/2/2019 23:04

Poulam M. Patel

In this trial, no patients received checkpoint inhibitors prior to vaccination but six patients (four with tumor and two with no tumor at study entry) received ipilimumab or nivolumab post-vaccination and three of these patients are still alive. Although these patient numbers are low, this suggests that SCIB1 vaccination may prime for responses to checkpoint inhibition.

[inanaco] 08/2/2019 22:51

PD-1 to T cell is not Antigen dependent ..

I have never posted 100% of patients would respond so don't add data that i have not mentioned



now you have just posted


"""" Until that point all you have is evidence that the mechanism of action and pre-clinical evidence in mice indicate that it should work. """"

thank you ....

"evidence that the mechanism of action""


so i will ask again

which trial has failed

SCIB1 in 35 patients

or

Keytruda an approved standard of care

[bermudashorts] 08/2/2019 22:37

Inanaco,

The link I posted was not intended to prove my point. When you have the vice president of Pfizer giving an overview of the state of therapeutic cancer vaccines then I would have thought it's of interest to anyone invested here. However there are several parts that reinforce my original points which were that you can't say Scancell is proven based on results in HPV cancers and that in fact you can't say anything is proven until you have run clinical trials and have the evidence. Until that point all you have is evidence that the mechanism of action and pre-clinical evidence in mice indicate that it should work.

Before I answer your post in full please can you clarify a couple of things.

1) 'you seem to think that is Antigen dependent ... its NOT' - how can it not be antigen dependent? For any vaccine to be effective - even with PD-1 it needs to target the correct antigens?

2) Based on your findings are you predicting that 100% of patients in the SCIB1 combination trial will respond? If not why might they not respond?

Finally, I have no problem with you discussing the science. I used to enjoy bouncing ideas in discussions with you. What I object strongly to is the no risk type language that you use and the raising of expectations. Moreover it actually detracts from your posts.

[inanaco] 08/2/2019 21:36

Bermuda

You still have not understood the posts ...

and that link rather than giving your opinion merit weakens it ...

they highlight the importance of the vaccines ability to

T cells that strongly recognize these antigens may have been removed from the immune repertoire by central and peripheral tolerance. Thus, a cancer vaccine must “break tolerance” by stimulating the low affinity or rare TAA-reactive T cells that remain.24 Strong adjuvants, co-stimulators, and repeated vaccination have been used to amplify the activation and expansion of self-antigen-reactive T cells,25 and this is particularly important for low-affinity T cells. Even with such enhancements, for many TAA-directed vaccine clinical trials the immune response, while detectable, does not appear to be strong enough to achieve significant efficacy.

so the Key is the "cross presentation route " for High Avidity T cells ..

they are proven to work .. those lung mets did not disappear on their own ..

My post relates to the Mechanism of action ... the synergy between the T cell and the PD-1 MAB

you seem to think that is Antigen dependent ... its NOT which means its not cancer type dependent ...

how the cancer reacts to Immunobody is Known ... Ifn-y production which upregulates PD-ligand on the cancer .. T cell is now Turned OFF

then you go on to post



5) You have not done a full risk assessment for SCIB1 - not one of us has the knowledge or expertise to do that.

----------------------------------------------------------------------------------

I have done it to the best of my ability .. if no other "expert" is available on here then surely my attempt is valid as nobody else even attempts it or is capable of questioning it ..

what interesting is, you are now claiming that nobody on here should question the science as none of us are experts .. ?

so why did you ask me to translate the patent ... ?

and indeed why have many of the debates we have had like the adjuvant debate turned out that my understanding was absolutely spot on ...

the issue in my mind is how do you evaluate who is an expert if you are not one ?

In all the years i have been learning the process which posts have i actually got very wrong on the science .. as every statement is backed up with evidence and explained

----------------------------------------------------------------------------------

Have a serious think before you reply ..

because PD-1 is being approved in more than one cancer indication ... which means the same immunosuppressive environment across certain cancers are similar

SCIB1 and 2 ... are engaging that environment

[ivyspivey] 08/2/2019 21:35

I know link is the same but if you click on mine goes straight to Cancer Vax Antigengs

[ivyspivey] 08/2/2019 21:32

Nice article Boom.
Found this bit interesting

[bermudashorts] 08/2/2019 20:37

Coincidentally a very comprehensive review 'Turning the corner on therapeutic cancer vaccines' was published today by Nature's npj vaccines journal. The author is Robert Hollingsworth, CSO and VP of Pfizer's cancer vaccines Division so also perhaps an insight into the thinking of big pharma.

No mention of, or references to Moditope or ImmunoBody but several sections are highly relevant and give a good perspective of the field as a whole.

[bermudashorts] 08/2/2019 16:27

Inanaco

Please stop making incorrect assumptions.

1) A primed and activated T cell generated by SCIB1 vaccination targets different antigens from one generated by Inovio's vaccine - they ARE different.

2)I didn't once state that T cells were specific to particular types of cancer. I said that you couldn't assume a vaccine that worked in HPV head and neck cancer would work in melanoma. That's because they target different antigens and the tumour microenvironment may be completely different with different immuno-suppressive mechanisms. With hindsight I should have spelled that out but didn't think I'd need to.

3) All you have done in all of your posts is describe the mechanism of action for PD-1 and cancer vaccines. The very reasons why Scancell believe there is merit in carrying out the combination trial. To even contemplate the idea that you can google your way to finding a mechanism of failure on the internet is just bizarre.

4) To be clear, even the World's leading experts don't yet know why some patients respond to PD-1 and some don't. It appears that high levels of PD-L1 increase the likelihood of response but some patients with very low levels respond and some with very high levels fail to respond.

5) You have not done a full risk assessment for SCIB1 - not one of us has the knowledge or expertise to do that.

[tosh123] 08/2/2019 12:48

Gazza,
you mean i may have been responsible for the origins of a blossoming loving relationship ? Im touched.
I think they would have found each other in the end anyway... as with any good relationship, theres always a giver and a taker, and that protocol fits very nicely in this instance.

[gazza] 08/2/2019 12:41

tosh, if you believe in ying and yang that was your fault! lol.

[tosh123] 08/2/2019 11:37

Dear oh dear, C7 is now so far up a certain persons back passage that all one can see of him are his shoes laces. What a creep... Honestly, what a pile of old pony.

They deserve each other.... The blind leading the blind, if ever i saw it.

[miavoce] 08/2/2019 11:19

Terror,

no problem with the first 4 points, but what do you mean by 'lost their way'....trial preparations are underway, albeit slowed by technical issues, and CRUK are delivering SCIB2 trial, patents reaching conclusion...I believe this is is line with what they said they would be doing ??

[oldnotwise] 08/2/2019 11:09

Loz, sorry, I see the story's changed again.
Please completely ignore my 19564...
Teach me to read stuff and believe it!!!
ATB

[terror] 08/2/2019 10:58

Nothing much has changed.

SP still falling

TurkeyFan gets told to shut up from C7

TurkeyFan slopes off in a huff

Scancell look to have lost their way

[the real lozan] 08/2/2019 10:09

The REALITY of 'The Garden Path'.. of trHYPE -
WHY do *WE ALL* think, that -
My OPEN INVITATION...to HIM, HIS BUY,BUY,BUY SCAM CLUB members,ANY of HIS 'victims',or ANYONE else...to 'show *US ALL* {Point*US ALL* in the direction} = = =
WHERE /WHEN inane'n'co "Got ANYTHING RIGHT"
.
Despite the months/years of this OPEN INVITATION....WHY are *WE ALL* waiting for ONE item of evidence ???
WHY CAN this be ???
One thing is CERTAIN...IF any such 'evidence' existed...*WE ALL* would have been 'made AWARE' of it...long ago
Perhaps = HE is too 'modest' to AFFIRM...WHERE/WHEN HE "GOT ANYTHING RIGHT"

[oldnotwise] 08/2/2019 09:53

Loz, it seems Elsie didn;t buy in by listening to anything on the MFFF after all. He says he bought in on 21st Aug 2012.....
"Yep, it was long before i even knew there was BBs, it followed after a good article. I think after selling a small ZOL holding I bought 7k shares at £3k. Roll on the times!!!"
So The MFFF had no involvement in his original investment.
So REALLY Loz .. fancy suggesting he was involved in all that!!
:-)
ATB

[the real lozan] 08/2/2019 09:21

The 'good old days' -
I see Elsie / M F F F, looking back 'fondly' to 2012...The year inane'n'co introduced sooo many 'sheeple' to 'The Garden Path'...of trHYPE
The same year, inane'n'co began to provide PROFITS for the WISER,more ASTUTE.. who spotted the opportunities 'The Garden Path'..of trHYPE = provided
.
HE still leads the 'lost' on 'The Garden Path..of trHYPE
Unfortunately for them, it leads to 'AN UNDERWATER SWAMP' ...they CAN't get out of.