WHAT IS
The Coxsackie Group B3 Virus Strain CVB3 PD-0
- Doesn’t cause severe side effects.
- Could potentially be targeted to several types of cancer.
- It can potentially become a platform for the creation of new (more effective) virus strains.
- Patent of 2017.
- Possibly should be used with other recognized treatments.
- Partial lysis of cancer cells, i.e., does not lead to complete healing. It is only prolong the patient’s life.
The Fundamental Indication
Colorectal cancer
Additional indications
- Pancreatic cancer
- Lung cancer
Inventors
Henry Fechner, DVM \ Ahmet Hazini \ Vanessa Brueckner
Patent owner
Technical University of Berlin
Patent number
US 10,639,337
Primary financing
Innovative Medicines Initiative 2 (IMI2-JU) under grant agreement №115797 INNODIA
Technology copyright holder
NIVIRON INC based on an option contract giving exclusive rights to obtain rights to the technology
BRIEF DATA
Conducted studies
- Viral plaque assay
- Cell killing assay
- Heparin inhibition assay
- HS6ST2 quantification
- CVB3 RNA quantification
- Flow cytometric analysis of CAR and DAF expression
- In situ hybridization
- DLD-1 cells (5×106 cells) were inoculated s.c. into the right and left flanks of 6-week-old female Balb/C nude mice. Tumor burdens were measured daily by hand caliper.
- CVB3 strains were injected intratumorally at a dose of 3×106 plaque forming units (pfu) per animal into one of the tumors when the tumor size reached 0.4–0.5 cm
The following analyses were applied
- Histopathological analysis
- Statistical analysis was performed with Graph-Pad Prism (GraphPad Software, Inc., La Jolla, CA)
All animal experiments were performed in accordance with the principles of laboratory animal care.
RESULTS
of oncolytic efficiency and safety of the strain PD
- No side effects caused by the virus were detected in animals treated with the CVB3 PD-0 strain
- No systemic infection of CVB3 PD-0 was detected, the virus could not be isolated from the organs of these animals.
- PD-0 is non-pathogenic for immunocompetent mice
- PD could infect colorectal carcinoma cell lines in vitro and it had the high efficacy. In vivo administration of PD in a xenograft mouse model of colorectal carcinoma resulted in strong reduction of tumor growth. PD showed a promising safety profile.
- Intratumoral injection of tumor-bearing nude mice with PD led to significant inhibition of growth of the injected tumor. Similar growth suppression was also observed for the distant, non-injected subcutaneous tumor.
- PD-infected animals showed a significantly prolonged survival. All six animals treated with PD were alive 10 days after intratumoral virus injection, and five of them showed a normal physical state, similar to the untreated negative control group. One of the PDinfected animals (PD-M1) showed slower movement and lower body weight compared to the other PD-infected animals.
- Virus in the tumors of PD-infected animals was detected at the level (between 3.2 and 7.2 · 106 pfu/g) in the primary injected tumor. In two of six investigated animals, PD was not detected in the untreated tumor.
- In situ hybridization confirmed the presence of viral genomic RNA in the tumors of PD-infected animals, aswell as the absence of virus in untreated tumors of two PD-infected animals, which were also negative when measured for replicating virus.
- PD showed strong cytolytic activity in DLD1, Colo680h, and Colo205 and moderate activity in Colo320 and LS174T.
- PD can use N- and 6-O-sulfated HS to attach and infect cells.
COMPARISON
of PD efficacy with CVB3 variant H3N-375/1 TS and with CVA21 on pancreatic carcinoma cell lines and melanoma cell lines
was engineered at the Technical University of Berlin by a team of scientists led by Henry Fechner and Ahmet Hazini. CVA21
is an investigational virus-based therapy developed by Viralytics. An inventor is Professor Darren Shafren.
Oncolytic activity of PD was shown in colorectal carcinomas. No comparision with other oncolytic viruses was done. Aim of the study
CHARTS
PD against colorectal carcinoma cells
Cytotoxicity
Growth curve
PD is most potent in colorectal carcinoma cells
CHARTS
PD against melanoma cells
Cytotoxicity
Growth curve
PD is more potent than H3N-375/1TS. Compared to CVA21 it is similar (in individual cell lines it is better (SK-Mel-19), in others CVA21 is better (A-375))
CHARTS
PD against pancreas carcinoma cells
Cytotoxicity
Growth curve
PD is most potent in pancreas carcinoma cell lines
PD has strong oncolytic activity in pancreas carcinoma cell lines and melanoma cell lines
PD has higher cytotoxic activity than H3N-375/1 TS and CVA21 in colorectal cancer and pancreatic cell lines. The virus also has a higher cytotoxicity than H3N-375/1TS in melanoma cells, whereas it is comparable to CVA21 in melanoma cell lines.
Also, these results give grounds to believe that the PD virus, in addition to colorectal carcinomas, may also be promising for the treatment of melanoma and pancreatic cancer.
Besides colorectal carcinomas PD may also be promissing for treatment of melanoma and pancreas carcinomas
