Immonotherapy Overview

[Javelin18]

I was inspired by Scout4answer's post on CAR-T to do some more research. I came across an overview of current immunotherapy approaches. It has a lot less jargon than most research papers.

ncbi.nlm.nih.gov/pmc/articl...

[MrG68]

I haven't looked at this, but noticed there was quite a large conflict of interests. Something you should take into consideration.

[Javelin18 in reply to MrG68]

Thanks, I hadn't noticed that. I've read through most of it, and it appears to give a top level summary of the range of research.

[Schwah]

I read it all. To be honest it’s kinda depressing. They keep hitting dead ends where they expected success. Hope it gets better. I have a special interest in immuno therapy because I recently did Provenge even though I’m hormone sensitive. I spent a lot of time researching it including talk to the company and a number of doctors at Ucla and otherwise who have delivered this medication. Although Provenge only showed a median Survival of 4.1 months, further review of the data showed some interesting things. Primarily, they broke it down Into various tranches based upon the starting PSA count. And every tranche, the lower the PSA at the start, the larger the survival advantage over the control group, with the same starting PSA. At the lowest PSA (under ten, I believe) the median survival advantage jumped to over 14 months.

Schwah

[Javelin18 in reply to Schwah]

That's interesting information about the correlation between PSA and effectiveness. I like the idea of dendritic vaccines and CAR-T since they stay in the system.

I guess it's frustrating that they haven't found the answer to immunotherapy, but I'm encouraged by the fact that they seem to be looking in right place. In my view the immunosuppressive environment is the thing that is keeping the immune approaches from working. I think it requires a combination approach. Something like a small molecule, vaccine, CAR-T or BITE combined with checkpoint inhibitors and suppression of macrophages.

I'm not sure they will get there in time for me, but I think they will get there soon.

[Schwah in reply to Javelin18]

So couple of other things I learned from my investigations into Provenge. Are you back (or still on) Lupron and Xandi ? If not you should re start. The studies showed that men who did Lupron with the Provenge had a much higher amount of the killer t-cells in their blood a year later than those who did not. Also did you have any visible mets? If so, you should do SBRT to those mets ASAP. The thinking is that the dying cancer cells will rev up the Provenge produced killer t-cells to do more killing of the cancer cells.

Schwah

[Javelin18 in reply to Schwah]

I'm not going to be receiving Provenge. I'm going to participate in a CAR-T trial. The protocol is different from Provenge, with pre-treatment to suppress immune cells prior to receiving the CAR-T cells. This removes immunosuppressive immune components so the T cells can work unimpeded.

[Schwah in reply to Javelin18]

Interesting that you say that. Dr. Scholz tried to convince me to add Yervoy to my protocol when I did Provenge for that exact reason. I probably should’ve done it but I chickened out because of the small percentage of pretty serious side effects. I think your trial I would use some thing similar to Yervoy. Let me know I’d be very interested

Schwah

[Javelin18 in reply to Schwah]

This trial uses flufarabine and cyclophosphamide to deplete existing immune cells. I think they spare dendritic cells, so they can naturally be primed by other antigens in the dying cells dying cells that express the the target antigen. This allows the T cells to recognize other forms of cancer that don't express the antigen.

[Fightinghard in reply to Schwah]

I just finished provenge 2 weeks ago. Overall was not too bad but i did have some interesting (to me) infusion reactions. Still having some reactions after 2 weeks that come and go. But slowly fading.

Hoping i get some positive results. My psa was still in the most favorable range at 2.1 and no known bone mets so keeping fingers crossed 🤞

Dr told me that everyone reacts differently to provenge. Happy to share more details about my personal reactions to the meds if anyone wants to know. Just pm me

[Schwah in reply to Fightinghard]

We’re you castrate sensitive or resistant ? I was hormone sensitive so forced to pay out of pocket. Also What were your “interesting” reactions. I had flu like symptoms for a few days in my third infusion only. Thx

Schwah

[Fightinghard in reply to Schwah]

SchwahCR. Side effects - Had very severe chills with whole body shaking head to toe during 3rd infusion. Thought I was in a deep freeze. Soon as drip stopped the shaking stopped in a couple mins. Right after each of the the cell collection cycles i had episodes of sweating really bad for about an hour even while i was cool enough. Lasted about a week after each cycle

After infusion have had every day a hour or so of brain fog and low fever, usually in later part of day. This seems to be lessening a bit every day now. Good.

PA told me that they think some patients react to the change/imbalance of the cell types in the blood until body has time to readjust the mixture. This can take several weeks she said

Told you it was a long story 🤷

[Schwah in reply to Fightinghard]

Long but interesting how different treatments can have such varying side affects. Glad you’re getting better. And the study indicates that your low starting PSA level should allow you to benefit quite well from a Provenge.

Schwah

[MyDad76]

I’m Slovenian and last year there was a lot of talk here about this study. Hoping it will get approval soon.

onlinelibrary.wiley.com/doi...

[Javelin18 in reply to MyDad76]

I hadn't heard of that dendritic vaccine before, thanks for sharing the paper. I'm not sure if I read the report correctly, but it didn't seem to show increased survival. I'm wondering if it also has trouble overcoming the immunosuppressive environment.

[MyDad76 in reply to Javelin18]

To be honest, this paper is too “scientific” for me. But in popular press it was written in plain words it was clearly stated by main researcher that “ in general patients lived 16 months longer and that results were better in those patients who did not have mets”.

In case you would like to read the article with google translator help, I post the link here: rtvslo.si/zdravje/slovensko...

[CurrentSEO in reply to Javelin18]

biologydirect.biomedcentral...

here is the confirmation that it prolongs survival

I think it might be similar to Indian APCEDEN

[Javelin18 in reply to CurrentSEO]

Thanks for the link. It also gives a nice description of immune system interactions with vaccines.

[Javelin18 in reply to CurrentSEO]

The effectiveness looks to be much greater than Provenge or Apceden. If I recall correctly, Provenge primes Dendritic Cells (DC) with a single antigen, and Apceden uses two.

This DC vaccine uses the patient's original tumor sample to bind all antigens with the DC. It also looks to modify the immune system response to decrease immunosuppression. Looks very promising.

[CurrentSEO in reply to Javelin18]

aHyC - Efficacy is greater than PROVENGE indeed. PROVENGE targets two antigens.

aHyC and APCEDEN looks similar to me, because both of them target broad spectrum of antigens based on patient tumor tissue. APCEDEN also claims 12 month extended survival, PROVENGE- 4 months.

[CurrentSEO in reply to MyDad76]

thank you!

[Javelin18 in reply to MyDad76]

CurrentSEO found a good paper describing it in simpler terms. I think this is worth you creating a separate post, and pointing people to the paper he found.

It looks like a breakthrough, and a separate post would give it more visibility.

[CAMPSOUPS]

Truly appreciate this contribution.Nice that this was just published a couple weeks ago too.

Some naysayers here among our brothers but I am looking at this optimistically.