Member Info for RayPointer

Yes, I see Pastorix could be very valuable and the previous RNS did indeed identify a number of compounds able to attack the CTCs once specific targets have been identified.

But it all seems to be about trying to stem the tide as do CIs IMO.
Now Scancell's products are all about destroying tumours and also creating a memory effect as a by product.

It has been suggested that Immunobody could work well on early stage cancer. So, a possible use in combination with Immunobody in early stage before metastasis takes place.

But Pastorix would not work in conjunction with Immunobody in the same way that a CI would. Here the synergy is obvious and will hopefully work superbly well.

As I understand if, Pastorix diagnoses targets on CTCs.
It would still need other products to attack the CTCs.

It has no affect on existing tumours, as I see it.

So, IMO, no direct synergy with Immunobody or Moditope.

Thanks lads for 2 great articles.
I've just skimmed through them but intend to do them both justice later.
ATB

I do remember reading an article saying that clonal expansion is regulated i.e. it reaches a certain level and the clonal expansion then stops.
Also, aren't activated TCells short lived? I seem to remember reading this as well,

This looks to be in addition to the fratricide you mention.
All seems a bit brutal to me. You would think the body would treat the TCells that have done their job as heroes rather than giving them the means to kill each other. Looks like they live short but exciting lives LOL

In contrast, the TCells that differentiate into memory cells are long living (up to 10 years)

http://www.portlandpresspublishing.com/sites/default/files/biochemist/Biochemist%20Immunology%20issue/BioFEB19Web_Choudhury%29.pdf

Posted previously by crumbs.

"CD4 T cells become activated and release IFN? which induces upregulation of MHC II expression by tumour cells. CD4 cells become further activated and kill tumour cells."

So further activation takes place at the tumour site. Part of that wonderful chain reaction.

The article below helps to define the difference between affinity (single binding) and avidity (multiple affinities)

https://en.wikipedia.org/wiki/Avidity

"In biochemistry, avidity refers to the accumulated strength of multiple affinities of individual non-covalent binding interactions, such as between a protein receptor and its ligand, and is commonly referred to as functional affinity. "

Therefore a single TCR can bind to its target antigen with high affinity but the avidity may be low since few TCRs in total have bound themselves to the target antilgen

https://www.sciencedirect.com/science/article/pii/S1074761300804902

"There are approximately 10 to the 5 (100,000) TCRs expressed on the surface of a cytotoxic T lymphocyte (CTL), and it has been suggested that engagement of anywhere from 3–400 TCRs per cell may suffice for CTL activation"

So considering a TCell binding to an APC

Activation may take place with a relatively low number of TCRs binding but the chances increase with number and also the length of time the binding is maintained.

In addition, once activated, the TCells must also show high avidity when binding with the target (tumour cell).

This is interesting since Lindy always emphasises high avidity in her talks about Immunobody and Moditope.

Mrs May would die for a back stop like SCIB1

Good to hear Wig.
Don't forget the Modi1 trial as well.
If we are at the stage of producing the tox report, this trial may also start soon.

"Genentech not holding back on splashing the cash on immuno onco deals this year!"

Kind of reminds you of their search for targets that Ira was involved with.
Quantity not quality seems to be the Genentech motto.

Maybe 30 patients with resected tumours would have done the trick.
Many statisticians believe 30 to be a minimum sample to make the figures meaningful.
But, there is a lot of debate around this.

https://www.researchgate.net/post/What_is_the_rationale_behind_the_magic_number_30_in_statistics

or just a simple pump and dump operation

Yes, I agree 100%.
The other statistic that is pretty amazing is that prior to treatment there were 43 separate surgeries.
Post treatment only 1 was necessary.

Actually looking at page 69 I will use the 3rd column (placebo) which has a 5 year survival rate for phase 3 patients only (we had 44% phase 4 in our trial and a much higher median age,
I will try to redo the calculation tomorrow with a revised expected 5 year survival rate.

Thanks again crumbs, page 69 looks like if it for the resected patients only (87.5% OS is 14/16)
Anyway, it is probably better to stick to these patients only and that is what I have done.

Yes, I know.
Whatever calculation is made has to be taken with a pinch of salt.

So if we use the swimmer chart, which I agree is probably the best option, I make the probability of this happening by chance is

16! / (2! x 14!) X x ** 2 x y ** 14

where y is the 5 year chance of survival
and x is the 5 year chance of not surviving

both expressed as fractions

so, for simplicity (for now) if we set both x and y to 1/2 (i.e. 50% chance of survival and also 50% chance of not surviving

this gives an answer of 120/65536 = 0.0018 or 0.18%

what I am missing is the 5 year survival rates of phase 3 and phase 4 melanoma patients with tumours removed.

So I have taken the most optimistic figure of 50% from

https://www.melanomauk.org.uk/about_melanoma/statistics/

"Stage 3
As you might expect, the survival statistics fall with these more advanced stages of melanoma. Between 4 and 5 out of every 10 people (40-50%) diagnosed with stage 3 melanoma will be alive 5 years later.

Stage 4
Understandably, the survival statistics are lower than for stage 3 melanoma. Between 2 and 3 out of every 10 people (20-30%) diagnosed with stage 4 melanoma will be alive 5 years later."

A very rough calculation so should be taken with a pinch of salt but I have tried to err on the conservative side.

Thanks crumbs
I was hoping to calculate the probability of the 5 year survival results being achieved purely by chance using 35 patients.
I will do the calculation based on the famous swimchart instead.

Talking of the SCIB1 trial, were the 5 year results of all 35 patients ever published.
The reason I ask is that 35 is far more statistically significant that 16.
In fact many statisticians like to see a sample of at least 30 but some disagree.

Yes I know Inan

But we don't know if a collaboration between all or selected GC team members exists or is being discussed.
Its a case of "watch this space"

Hi VanVan
Scancell are not in collaboration with Genentech as far as I know.
ATB

So Ivy

MUFC v NUFC

Who do you shout for?

Hindsight tells us that it may have been better to run the trial in UK/Europe.

However, Scancell can do nothing about the current delay apart from offering to support Ichor in getting those questions answered to the FDA's satisfaction.
It is unlikely that a UK trial would start whilst the FDA still have unanswered questions. I think Sally has already said that.

So, given the current situation, I don't see how more resources diverted to the SCIB1 combo trial would help.
It is good to have the extra irons in the fire in this situation.