Virotherapy
WHAT IS VIROTHERAPY?
treatment using biotechnology to convert viruses into therapeutic agents by reprogramming viruses to treat diseases
UNDERSTANDING VIRUSES
Vaccines contain dead viruses (containing no DNA or RNA, only the capsid) which are used to prevent viral infection and contain outbreaks. In Biotech we can viruses as vectors to carry altered DNA to specific target cells. “Viral vectors are tools designed to deliver genetic material into cells. Viruses have evolved to develop specialized mechanisms which transport their genomes inside the cells they infect. Modified viruses are used as viral vectors (or ‘carriers’) in gene therapy, protecting the new gene from degradation while delivering it to the “gene cassette” in target cells. Viral vectors effectively coerce target cells to accept and separate the new gene from the virus particle and transport it to the cell nucleus, for example. The target cells begin using the new gene to perform its function. Most of the essential genes in viral vectors are missing due to genetic engineering which means viral vectors are often grown in culture with special cells that provide the missing viral proteins to successfully package the therapeutic gene(s) into virus particles. There are several types of viral vectors that can be used to deliver nucleic acids into the genetic makeup of cells including retrovirus, lentivirus, adenovirus, adeno-associated virus and herpes simplex virus–each with its own advantages and disadvantages for specific applications.”
THE 3 BRANCHES
Click each icon to read descriptions of each branch.
ONCOLYTIC VIRUS
“Oncolytic virotherapy is an emerging treatment modality which uses replication competent viruses to destroy cancers. Advances in the past two years include preclinical proof of feasibility for a single-shot virotherapy cure, identification of drugs that accelerate intratumoral virus propagation, new strategies to maximize the immunotherapeutic potential of oncolytic virotherapy, and clinical confirmation of a critical viremic thereshold for vascular delivery and intratumoral virus replication. The primary clinical milestone was completion of accrual in a phase III trial of intratumoral herpes simplex virus therapy using talimogene laherparepvec for metastatic melanoma. Challenges for the field are to select ‘winners’ from a burgeoning number of oncolytic platforms and engineered derivatives, to transiently suppress but then unleash the power of the immune system to maximize both virus spread and anticancer immunity, to develop more meaningful preclinical virotherapy models and to manufacture viruses with orders of magnitude higher yields compared to established vaccine manufacturing processes. Oncolytic viruses are structurally and biologically diverse, spreading through tumors and killing tumor cells by multiple mechanisms and with different kinetics. Because of their large size and immunogenicity they are constrained by physical barriers and by host immunity, but they can also cross-prime and amplify antitumor immunity, serving as a cancer immunotherapy.”
VIRAL VECTORS
“Applications of viral vectors have found an encouraging new beginning in gene therapy in recent years. Significant improvements in vector engineering, delivery, and safety have placed viral vector-based therapy at the forefront of modern medicine. Viral vectors have been employed for the treatment of various diseases such as metabolic, cardiovascular, muscular, hematologic, ophthalmologic, and infectious diseases and different types of cancer. Recent development in the area of immunotherapy has provided both preventive and therapeutic approaches. Furthermore, gene silencing generating a reversible effect has become an interesting alternative, and is well-suited for delivery by viral vectors. A number of preclinical studies have demonstrated therapeutic and prophylactic efficacy in animal models and furthermore in clinical trials. Several viral vector-based drugs have also been globally approved.”
VIRAL IMMUNOTHERAPY
"Unlike traditional vaccines, in which attenuated or killed virus/bacteria is used to generate an immune response, viral immunotherapy uses genetically engineered viruses to present a specific antigen to the immune system. That antigen could be from any species of virus/bacteria or even human disease antigens, for example cancer antigens. Vaccines are another method of virotherapy that use attenuated or inactivated viruses to develop immunity to disease. An attenuated virus is a weakened virus that incites a natural immune response in the host that is often undetectable. The host also develops potentially life-long immunity due to the attenuated viruses similar to the actual virus. Inactivated viruses are killed viruses that present a form of the antigen to the host. However, long-term immune response is limited. There are two general approaches to develop these viruses using applied evolutionary techniques: Jennerian and Pastorian. The Jennerian method involves selecting similar viruses from non-human organisms to protect against a human virus while Pastorian methods use serial passage. This Pastorian method is very similar to directive evolution of oncolytic viruses. Selected viruses that target humans are passed through multiple non-human organisms for multiple generations. Over time the viruses adapt to the foreign environments of their new hosts. These now maladapted viruses have minimal capacity for harming humans and are used as attenuated viruses for clinical use. An important consideration is to not reduce the replicative ability of the virus beyond the point where the immune system response will be compromised. A secondary immune response would therefore be insufficient to provide protection against the live virus should it be reintroduced to the host."
