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
