VCN-01 , SYN-004, SYN-020: Hope for oncolytic viral therapy in cancer treatment

Theriva Biologics, Inc. is a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need. It is advancing a new oncolytic adenovirus platform. Its candidates are VCN-01, SYN-004 (ribaxamase) and SYN-020. VCN-01 is an oncolytic adenovirus designed to replicate selectively and aggressively within tumor cells, and to degrade the tumor stroma barrier that serves as a significant physical and immunosuppressive barrier to cancer treatment. SYN-004 (ribaxamase) is designed to degrade certain commonly used intravenous beta-lactam antibiotics within the gastrointestinal (GI) tract to prevent microbiome damage. SYN-020 is a recombinant oral formulation of the enzyme intestinal alkaline phosphatase produced under current good manufacturing practice conditions and intended to treat both local GI and systemic diseases. Its research programs include VCN-11 Albumin Shield Technology and SYN-006, SYN-007, other oncolytic virus.

Introduction

For several years now, oncolytic viral therapy has been gaining a lot of interest as a promising strategy in cancer therapy. The strategy behind is that genetically modified virus is being used on cancer cells rather than normal cells to kill them and leave the normal cells untouched. VCN-01 is an oncolytic adenovirus that has been consciously developed to have the potential to grow and spread actively within the cancer tissues only. Together with SYN-004 (ribaxamase), SYN-020, and other similar agents, their use is under study as adjuvants to oncolytic viral therapy.

Oncolytic Adenovirus: VCN-01

Oncolytic adenoviruses are involved in developing virus which selectively infect and kill cancer cells. Adenoviruses are desirable, non-enveloped viruses originating from humans and their common major sites of attachment are the respiratory and the gastrointestinal tracts. Short non-integrating oncolytic adenoviruses have been engineered with tumor specific targeting property, which facilitates the viruses to enter the tumor cells with high efficiency and causes their death through different pathways. VCN-01 is another oncolytic adenovirus that is being developed by Viral Clear Pharmaceuticals and which has been tested in pre- clinical studies.

VCN-01 has targeted action on coxsackievirus and adenovirus receptor (CAR) which is on tumor and normal cells. Nevertheless, it was discovered that tumor cells reduce the amount of CAR that the oncolytic adenoviruses, such as VCN-01, can take advantage of. Due to this challenge, researchers have designed VCN-01 that has high binding specificity to CAR allowing it to attach to the cancer cells and replicate with preference. The improved binding increases the effectiveness of the treatment because it enables VCN-01 to break down tumor stroma barrier effectively; this is a significant physical and immunosuppressive barrier to cancer treatment.

Synthetic Immunomodulatory Agents: SYN-004 and SYN-020

Therefore, oncolytic viral therapy with VCN-01 can also be combined with synthetic immunomodulatory agents including SYN-004 and SYN-020. SYN-004, specifically referred to as ribaxamase, has elucidated the ability to degrade the matrix within tumors, allowing immune cells and VCN-01 to enter within the tumor more effectively. On the hand, SYN-020 is a TLR agonist that will be used in the stimulation of the immune response following oncolytic viral therapy treatment. TLRs are Type II transmembrane proteins expressed mainly on the cell surface as receptors most important for immunity and inflammatory responses. When stimulated by ligand SYN-020, TLRs can induce release of pro-inflammatory cytokines and chemokines which will increase the ability of VCN-01 in eliminating cancer cells by enhancing the infiltration of immune cells at the tumor site.

Opportunities and Advantages of Limited Data Set or VCN-01, SYNOVAC OR SYN-004, and SYN-020

Thus, the use of VCN-01 together with SYN-004 and SYN-020 has several theoretical benefits compared with traditional treatments of cancer. These agents reduce the density of the tumor stroma and increase the immune cell infiltration into the tumor mass, resulting, therefore, in the more effective and selective delivery of VCN-01 to cancer cells, and consequently the destruction of the tumor. Also, through the enhancement of immune system response by SYN-020, the bodies immune system is trained to better defend against cancer cells and thereby be capable of preventing the relapse of tumors.

Of course, there are still several advantages that has yet to be discovered, which include: Another advantage might be that the treatment approach used alongside other treatments for cancer may also complement it. Oncolytic viral therapy can be applied either as an adjuvant to the conventional approaches of antitumor treatment, which may include chemotherapy, radiation therapy, or immunotherapy, or as an additional step in combining it with other types of treatment. This combinatorial strategy then enables the clinici an to take advantage of the potency offered by the use of a number of treatment forms, to produce superior clinical results for cancer patients.

Phase 0, I, and II Trials

Mice and rabbit studies have demonstrated that VCN-01, SYN-004, and SYN-020 have potential for prevention of chemotherapy-induced diarrhea. The in vitro experiments showed that VCN-01 can selectively infect cancer cells and induce cell apoptosis, and that SYN-004 and SYN-020 can boost immunogenicity and allow immune cells to enter cancer tissues. Experimental in vivo exams with these agents have also revealed that their amalgamation can provoke marked regression of tumors and increase the survival rates of animals with cancer.

But clinical trials are ongoing to determine how effective this approach is as an avenue to treatment. These trials will yield good data on the proper dose and frequency of use of VCN-01, SYN-004, and SYN-020 in patients with cancer, side effects included. Also, more of such trials will assist in defining the best way to use these agents in coordinating CPX therapy and find probable patient subsets, which will benefit from the use of this therapy.

Conclusion

Therefore, the down-regulation of the target VCN-01, SYN-004, and SYN-020 may provide a potential way to advance oncolytic viral therapy for cancer treatment. By preferentially killing cancer cells and–in addition–disintegrating the tumor stroma as well as activating the immune system, these agents can enhance the efficacy of ‘conventional’ oncolytic adenoviruses such as VCN-01. Therefore, as trials go on, there should be more revelations on the efficiencies and constrains of this modern method of cancer treatment to help in future research.