Analysis of the mechanism of action of
REBACIN®
Owing to the complexity of persistent hrHPV infection, the development
of anti-hrHPV drugs and therapeutic vaccines is still in progress
despite many attempts. The results of three different modes of clinical
evaluation in clearing persistent hrHPV infection were highly
consistent: the negative conversion rate of REBACIN®intervention was 62–70%, whereas the self-negative conversion rate of
the control was 13–20.0%. All clinical studies confirmed that
REBACIN® is a safe and effective non-invasive clinical
intervention for the clearance of persistent hrHPV infection.
Recently, Murakami et al.
performed a comparative analysis investigating the specific requirements
for HPV16 and HPV11 genome replication in ”infected” basal-like
keratinocytes. They observed that the HPV16 genome, but not HPV11, is
maintained in keratinocytes during tissue culture; however, in the
presence of HPV16 E6 and/or E7, HPV11 genomes also replicated in
cultured tissue cells.25 This finding indicates that
hrHPV E6/E7 oncogenes play a pivotal role in enabling maintenance of
hrHPV genome replication in host cells. If the hrHPV E6/E7 oncogene is
suppressed, the viral genome cannot continue to replicate and the virus
is thereby eliminated. Thus, this finding provides further evidence that
REBACIN®eliminates persistent high-risk HPV infection via targeting and
inhibiting the expression of hrHPV E6/E7 oncogenes.
A pioneer clinical study
in regression of hrHPV associated HSIL
It is well known that hrHPV infection and integration of the hrHPV
genome into the host chromosome are key early events in tumor
progression of cervical lesions. The viral oncoproteins hrHPV E6 and E7
are responsible for initial changes in epithelial cells. Progression
from hrHPV infection of epithelial cells to invasive carcinoma is a
prolonged process, taking at least 15–20 years for transition from
precancerous lesions to invasive carcinoma. During this period
epigenetic changes in oncogenes and tumor suppressor genes occur. After
HPV infects the host’s basal squamous cells, it evades the host’s immune
system and continues to replicate in the basal epithelial cells.
Cervical intraepithelial neoplasia grade 1 (CIN 1) is the stage at which
the virus continues to infect cervical cells. CIN 1 lesions may progress
to CIN 2/3 within 2–3 years of infection.26Therefore, the regression of cervical lesions can be promoted by
inhibiting the expression of hrHPV E6/E7 oncoproteins, restoring the
activity of p53 and pRb tumor suppressors, restoring cellular innate
immunity, and recovering the repair function of cellular DNA. Based on
the previous finding that
REBACIN® can
effectively target and inhibit the expression of viral E6/E7 oncogenes,
several clinical exploratory and pioneering studies have been conducted
on the regression of high-grade cervical intraepithelial neoplasia with
REBACIN® treatment.
REBACIN®-mediated
regression of HSIL
In a recent clinical observation of regression of HSIL (CIN2), 88.89%
(16/18) of patients with HSIL (CIN2) and persistent hrHPV infection
regressed after one to three courses of REBACIN®treatment, and exhibited clearance of hrHPV infection (Table
S1).14
Although variable rates of spontaneous regression have been reported in
patients with CIN2/3,27-29 it is difficult to verify
because of differences in patient enrollment and duration of clinical
observation. In the current study, 88.89% (16/18) of patients with HSIL
(CIN2) displayed not only regression but also clearance of hrHPV
infection, indicating that REBACIN® intervention is
indeed a potential non-invasive therapy for HSIL (CIN2) regression.
However, owing to the limitation of participants in this observation,
more data from prospective studies are required to accurately evaluate
the effect of REBACIN® on HSIL regression.
Combinative effect of REBACIN ® with
LEEP
In a previous investigation of patients with HSIL (CIN 2/3) and hrHPV
infection who underwent loop electrosurgical excision procedure (LEEP)
following REBACIN® treatment, 51 of 53 patients were
negative for both CIN and hrHPV infection during the 24-month follow-up
assessment. This 96.23% (51/53) disease-free rate was significantly
higher than that of 73.47% (36/49) in the LEEP control group. Two
patients in the REBACIN® treatment group showed
persistent HPV positivity and re-developed CIN during follow-ups,
resulting in a disease recurrence rate of 3.77% in the
REBACIN® group, while the recurrence rate in the
control group was 26.53% (Table S2).30 This study
illustrated that REBACIN® treatment in combination
with LEEP can effectively enhance the cure rate of high-grade cervical
intraepithelial neoplasia and significantly reduce relapse compared to
treatment with LEEP only.