Here is fantastic news for men who undergo an initial treatment for localized prostate cancer! In November, 2020 the U.S. Food and Drug Administration (FDA) granted Fast Track Designation to RV001, an investigational vaccine against prostate cancer recurrence after primary treatment. RV001 is manufactured by a Swedish pharmaceutical company called RhoVac.

Let’s look at the science. When prostate cancer (PCa) is still early and confined to the prostate gland, success statistics for an initial localized treatment are very favorable – as much as 95% or higher cancer control. This is called primary treatment because it’s the first intervention performed with curative intent. Treatments include surgery (radical prostatectomy), radiation (external beam or seed implants), or whole gland ablation (tumor destruction using extreme heat or cold). Note that after treatment, patients must still have annual PSA tests to monitor for recurrence.

Why does recurrence happen after treatment?

Sadly, even after an apparently successful primary treatment, cancer can still come back. It’s the nature of cancer itself. As with all tumor cancers, PCa starts when normal cells mutate into malignant (cancerous) cells. Eventually they begin to duplicate themselves (growth in numbers); they also have the potential to biochemically form more dangerous mutations (progression). As a tumor grows and progresses, its cells can break away and begin to spread via the blood and lymph system. This process is called metastasis. All primary treatments have the goal of removing or destroying every tumor cell so there’s nothing left to spread.

In some cases, however, microscopic cells have already escaped even before the primary treatment. These cells must overcome the many hurdles they face from the body’s immune defense system, but it is difficult to detect them until they have finally begun to cluster into one or more tumors somewhere else in the body. The first sign of this is usually a rise in PSA, which is called biochemical recurrence. Recurrence is scary, because so far there is no known cure for metastatic PCa.

Can metastasis be prevented?

This is where RV001 comes in! According to RhoVac’s website, RV001 is a type of immunotherapy vaccine that is “…designed specifically for preventing or eliminating metastatic cancer cells, irrespective of cancer type.”^[i] It uses the biochemistry of the metastatic cells to “pre-program” the immune system’s killer T-cells to assassinate them—a lethal hurdle that, it is hoped, no rogue cell can escape. Here’s how it works:

Metastatic cancer cells over-express a protein called RhoC. It is this protein that lends to the metastatic potential cancer cells their ability to migrate and infiltrate other tissue. RhoVac’s drug candidate, RV001, is an immuno-oncologic drug that is presented to the immune system as an antigen, stimulating T-cells to identify and destroy cells that carry this protein, i.e. metastatic or metastatic potential cells.^[ii]

In other words, the immune system is programmed to seek and destroy cancer cells that are identified by the protein they carry.

Is RV001 effective?

That’s a good question. In preliminary tests, it evoked a T-cell response in most patients. In fact, the basis for the FDA’s Fast Track Determination was a Phase I/II clinical trial that tested the investigational vaccine on 22 patients who had previously had a prostatectomy.^[iii] Each patient received an injection of RV001 every 2 weeks for the first six times, then five times every 5 weeks for a total treatment period of 30 weeks. During treatment and for a 13-month follow-up period, the men were monitored for drug safety and vaccine-specific immune responses.

As reported in Urology Times, “Overall, 18 of 21 evaluable patients developed a strong CD4 T cell response against the vaccine. The response durations all lasted at least 10 months after the patient received the last injection of RV001.” Although the primary outcome measure of the study was safety, which was achieved without any high-grade adverse events, the fact that there was a strong immunological response was like a scientific home run.

With these promising results, further evaluation of RV001 is being conducted in a double-blind phase 2 trial in patients who underwent a primary therapy with curative intent but who are experiencing biochemical failure (rising PSA). Participants will be randomized to either the vaccine or placebo. For this study, the primary outcome measure will time to PSA progression to evaluate the duration of a T-cell response.

All of us at Sperling Prostate Center congratulate the team of researchers who have accomplished the first step in what would surely be a breakthrough in PCa therapy. We join physicians and patients everywhere who hope that the ability to prevent PCa recurrence by short-circuiting metastasis is closer than we think.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

[i] https://www.rhovac.com/product-development/the-scientific-concept/
[ii] Ibid.
[iii] Schuhmacher J, Heidu S, Balchen T, et al. Vaccination against RhoC induces long-lasting immune responses in patients with prostate cancer: results from a phase I/II clinical trial. Journal for ImmunoTherapy of Cancer 2020;8:e001157.