Viral gene therapy for breast cancer: progress and challenges

Abstract

Breast cancer is the most common cancer in women all over the world. Furthermore, up to one third of breast tumors develop metastases that are resistant to standard therapies. Gene therapeutic strategies have been developed in order to specifically target cancer cells either directly or through the stimulation of antitumor immunity. Areas covered: This review describes the therapeutic strategies that are currently under development to treat this disease using engineered viral vectors including: adenovirus, adeno-associated virus, lentivirus, poxvirus, reovirus, baculovirus, herpesvirus and oncolytic viruses. Advantages and disadvantages of these multiple gene therapy platforms are discussed in detail. Expert opinion: Metastatic breast cancer is a perfect candidate for gene therapy approaches due to the presence of several tumor antigens and the aberrant expression of many molecular pathways. Oncolytic vectors are able to attack tumor cells while sparing normal cells and their activity is often enhanced by the administration of chemotherapy. However, more efforts are needed in order to reduce toxicity and to achieve better transduction efficiency. Improved preclinical models and a more critical patient selection for clinical trials, along with advances in gene therapy regulations, will surely facilitate the evolution of gene therapy for the treatment of metastatic breast cancer.

A double safety lock tumor-specific device for suicide gene therapy in breast cancer

“…Different approaches have been developed in gene therapy to treat breast cancer, including the transfer of toxic or pro-apoptotic genes. To date, most research into suicide gene therapy in breast cancer has focused on the use of viral vectors [5][6][7][8][9], mainly due to their higher transfection levels. Thus, herpes simplex virus thymidine kinase (HSVtk) gene has been delivered by an adenovirus in combination with ganciclovir as the first and most common strategy used in experimental and clinical studies of suicide gene therapy [10,11].…”

The Journey of in vivo Virus Engineered Dendritic Cells From Bench to Bedside: A Bumpy Road

“…This is exemplified by the recombinant vaccinia virus, which is based on the attenuated Wyeth strain. Another interesting asset is the fact that poxvirus-derived vectors are relatively easy to produce at high-titers and stability ( 43 ).…”

“…Adenoviruses are non-enveloped dsDNA viruses efficient at delivering DNA to both dividing and quiescent cells, like DCs. Furthermore, they can be readily produced with high titers up to 10 9 IFU/ml that can be concentrated to 10 13 IFU/ml ( 43 ). Early cancer vaccination studies used replication-incompetent variants (deletions in E1 and E3 region) of serotypes Ad2 and Ad5 encoding a range of TAAs.…”

“…Even though AAVs are less immunogenic than adenoviral vectors, antibody neutralization due to previous exposure of the patient to multiple AAV serotypes, remains a common limitation for successful gene therapy and repeated vaccination ( 43 , 140 ). Numerous AAV serotypes have been identified so far, with variable tropism depending on their route of administration ( 141 ).…”

Combining DNA Vaccine and AIM2 in H1 Nanoparticles Exert Anti-Renal Carcinoma Effects via Enhancing Tumor-Specific Multi-functional CD8+ T-cell Responses

“…Currently, the used delivery vectors containing retroviruses, adenoviruses, and lentiviruses have been widely applied in vaccine therapy (22)(23)(24). However, the safety concern of viral vectors on oncogenic potential, immunorecognition, and immune responses has limited their clinical applications (25,26). Therefore, safe and efficient vaccine carriers are key to clinical success of vaccine therapy.…”