Adenoviral Vector-Based Strategies for Cancer Therapy

Abstract

Definitive treatment of cancer has eluded scientists for decades. Current therapeutic modalities like surgery, chemotherapy, radiotherapy and receptor-targeted antibodies have varied degree of success and generally have moderate to severe side effects. Gene therapy is one of the novel and promising approaches for therapeutic intervention of cancer. Viral vectors in general and adenoviral (Ad) vectors in particular are efficient natural gene delivery systems and are one of the obvious choices for cancer gene therapy. Clinical and preclinical findings with a wide variety of approaches like tumor suppressor and suicide gene therapy, oncolysis, immunotherapy, anti-angiogenesis and RNA interference using Ad vectors have been quite promising, but there are still many hurdles to overcome. Shortcomings like increased immunogenicity, prevalence of preexisting anti-Ad immunity in human population and lack of specific targeting limit the clinical usefulness of Ad vectors. In recent years, extensive research efforts have been made to overcome these limitations through a variety of approaches including the use of conditionally-replicating Ad and specific targeting of tumor cells. In this review, we discuss the potential strengths and limitations of Ad vectors for cancer therapy.

Adenovirus Composition, Proteolysis, and Disassembly Studied by In-depth Qualitative and Quantitative Proteomics

“…First isolated in the early 1950s, HAdV has served as a model virus to elucidate the molecular basis of viral structure, replication, and pathogenesis (2)(3)(4), with notable contributions to the field of eukaryotic molecular biology (5,6). Most importantly, HAdVs are broadly employed in molecular biotechnology as gene delivery vectors and DNAbased vaccine vehicles (7,8). Nevertheless, these applications are partly hampered by the immune response elicited by the capsid proteins, as well as the difficulty in targeting specific cell types.…”

The effectiveness of the oncolytic activity induced by Ad5/F35 adenoviral vector is dependent on the cumulative cellular conditions of survival and autophagy

“…However, they also possess significant advantages, such as efficient transgene delivery, expression in both dividing and non-dividing cells and ease of propagation to high titers (1)(2)(3).…”

“…To overcome the non-specific transcription of adenoviral vectors, conditional replication of the adenovirus and specific targeting of tumor cells have been used (2). Briefly, these efforts can be categorized into two general approaches.…”

Treatment of Malignant Melanoma by Downregulation of XIAP and Overexpression of TRAIL with a Conditionally Replicating Oncolytic Adenovirus

“…Among them, adenovirus vectors have several advantages over other vectors; they can easily be grown to high titers and can efficiently transfer foreign genes into both dividing and nondividing cells (Volpers and Kochanek, 2004;Ghosh et al, 2006;Sharma et al, 2009). Conditionally replicating oncolytic adenovirus (CRAd) is a potential…”