Some amateur speculations on the Rhovac drug candidate, the cancervaccin RV001V, that recently failed in phase II. Just speculations…
As I understand… initially RV001V activates the bodys immune system to recognize “RHOC”, which is a protein only present on migrating cancercells. The goal is to eliminate migrating cancercells and thereby reduce/eliminate the occurrence of metastasis.
Source: RV001 - vetenskapligt koncept | RhoVac AB
Ok… but what, more precisely, is the meaning of the term “migrating”, in the Rhovac concept?
If I, as an amateur, were to guess… it would be clear that “migrating cancercells” of course includes such RHOC-presenting cancercells that (i) have left the primary tumor and are free circulating, perhaps in the blood. Probably “migrating cancercells” would also (ii) refer to such RHOC-presenting cancercells that are still within the primary tumor, not yet released?
But… what about a case when (iii) a distant metastas have allready been established? Does the action of RV001V also reach such “migrating cancercells” that have allready established a new and emerging metastas?
If NOT… if RV001V is NOT able to target allready established metastases… then it is perhaps logical (?) that the status of such allready established metastasis at the defined time for biochemical recurrence could be a highly relevant factor? With the potential to have effect on the outcome of the study?
So, what were the criteria for measuring new metastasis in the failed Rhovac study? The study protocol says that among the inclusion criteria were:
“Biochemical recurrence (BCR) within 3 years of radical prostatectomy (RP) or definitive RT and no distant metastasis by standard CT imaging and bone scintigraphy, or locoregional recurrence (including lymph nodes) assessed by CT or multi-parametric magnetic resonance imaging (MRI) and confirmed with negative biopsy in case of prior RT.”
Source: Study of RV001V in Biochemical Failure Following Curatively Intended Therapy For Localized Prostate Cancer - Full Text View - ClinicalTrials.gov
Ok… as I understand, the failed Rhovac study used CT imaging to define if distant metastasis had occurred at the time of biochemical recurrence. But… what if CT imaging is not sensitive enough to capture very small and emerging metastasis? What if there were a way to complement CT imaging, complement the information regarding possible metastases, and thereby be able to more precisely define differentiated patient populations at the time for biochemical recurrence?
And the term “biochemical recurrence” is also interesting. In the Rovac prostate study, the definition appears to be connected to the “doubling time” of defined levels of PSA.
The doubling time of PSA is also closely related to the primary outcome in the Rhovac study. But what if there are emerging metastasis unnoticed by CT imaging at the time for biochemical recurrence? As I understand, such distant metastasis outside of the prostate, will not generate any increasing PSA? And, if so, they will have no impact on the defined primary outcome of the study protocol?
In Per Olof Lundgrens 30-year study, the authors define some areas where TK1 could become useful, including:
“A possible area of use is the evaluation of the probability of metastatic disease at the time of biochemical recurrence.”
Source: https://onlinelibrary.wiley.com/doi/full/10.1002/pros.24335
As I understand, Per Olof Lundgrens study (published March 2022) is the first study from “the AroCell sphere” to mention the term “biochemical recurrence”.
And exactly this… “evaluation of the probability of metastatic disease at the time of biochemical recurrence” (from the Lundgren study) could, as I would like to propose 
, perhaps be a possible key-factor in the Rhovac case. Also noticeable is Per Anders Abrahamssons former role as a scientific adviser to Rhovac.
Of course, as an amateur I don´t understand these things… but sometimes it is interesting just to try and follow the “logic”… Just speculations. Maybe its all wrong… very wrong…