Vaccine Candidates of Interest--- pTVG-HP DNA Vaccine and pTVG-AR DNA vaccine-- Brothers with Different Targets

[NPfisherman]

The vaccines continue with pTVG-HP DNA Vaccine. This vaccine is currently in a Phase 2 clinical trial with Keytruda and comes from the University of Wisconsin, which seems quite involved in vaccine trials.

This is a cancer vaccine containing plasmid DNA encoding human prostatic acid phosphatase (PAP) (pTVG-HP) with potential immunostimulatory and antineoplastic activities. Upon administration, pTVG-HP plasmid DNA vaccine may stimulate the host immune system to generate a cytotoxic T lymphocyte (CTL) response against PAP-expressing prostate cancer cells. PAP or prostatic specific acid phosphatase (PSAP) is a tumor associated antigen (TAA) that may be overexpressed in prostate cancer. [from NCI]

In Phase I, the vaccine resulted in a marked increase of PSADT in 2/9 patients. There was a clear immune response CD8+T cell in patients and the vaccine looked promising--see below:

cancerres.aacrjournals.org/...

In a Phase 2 trial with the vaccine +Sipulcel -T compared to monotherapy, there was not a significant difference in effecting an immune response. In another comparison with GM-CSF, there was no improvement in metastasis free survival, but some evidence that the vaccine had effect on micrometastatic bone disease resulting in the current trials listed below:

cancer.gov/about-cancer/tre...

In one of the current trials, the vaccine will be combined with it's brother pTVG-AR DNA vaccine. The difference is that this brother is encoded to target the Androgen Receptor ligand instead of PAP. For its' initial Phase 1 in an 18 month trial, 47% of patients developed significant immunity with only 28% having PSA progression. In the conclusion in the trial, the following was stated, "Association between immunity and PPFS suggests that treatment may delay the time to castration resistance, consistent with preclinical findings, and will be prospectively evaluated in future trials. see below:

clincancerres.aacrjournals....

So why am I interested ?? In the one current trial, the 2 Brothers with 2 separate targets will be combined with Keytruda and GM-CSF boost against MCRPC. Will the two different targets result in multiple targeting T cells and other immune cells further boosted in penetrating the tumor microenvironment by the CPI-Keytruda ? Will we see PSA Progression Free Survival (PPFS) double with 2 separate targets resulting in an immune response in almost every patient?? Only time will tell, but the plot thickens as our knowledge of understanding the immune system increases.

Don Pescado

[GreenStreet]

Thanks once again. I had no idea about these particular trials. It looks like establishing the right combo is the most promising route.

[NPfisherman in reply to GreenStreet]

Very astute !!! That is the true challenge.....what combo will provide the most impact on Pca.....getting people remissions of length....ie:years and pushing the Grim Reaper into the rear view mirror a long way off....Immune response with memory T cell generation results in an attack on Pca for months.....increases PSADT (more time) and allows Science to discover more drugs, vaccines, etc... it is not JUST what they do for PCa....it is what they are doing for all cancers since drugs seem to be based on mutations, not cancer type...ie:BRCA 1/2 and PARPS.... last 5 years and there is a good chance you will last 5 more...

Fish

[TheTopBanana]

Thank you! So interesting. Which trial Do you find most promising?

[NPfisherman in reply to TheTopBanana]

Rhovac's RV001--- prolonged immune response is important, but more so....Metastasis....stopping mets is EVERYTHING !!....primary doesn't kill....secondary kills...stop metastasis and you are in a permanent remission essentially... I watch the drug Metarrestin for metastasis also....

clinicaltrials.gov/ct2/show...

It's finding the right combo....should RV001 be combined with stereotactic radiation and Xofigo for micromets (RAVENS trial) in oligometastatic patients for a possible cure, especially those patients that have no major mutations (had best results in ORIOLE trial). I think that would be most interesting indeed...

Combos will be the answer....

Fish

[GreenStreet in reply to NPfisherman]

Yes preventing Metastasis is the key. I am sure a combo will be found but the question is how quickly. The trials seem promising but it feels like we may just be in the foothills with regards to prostate cancer. If really serious money was put behind it like 20% of C19 research I wonder how quickly it could be done.

[NPfisherman in reply to GreenStreet]

Geez... I would be happy if they started funding PCa like Breast cancer....they give out 80 million more dollars annually for breast as opposed to prostate. Let that sink in for a minute... 72% more dollars... PARP inhibitors came about courtesy of breast cancer... we're getting their leftovers....

Agree that we are in the foothills/early stages...it will come, but how many die during the process.... saddening....

Fish