Potential and limitations of bacterial-mediated cancer therapy

Abstract

Bacterial-based tumor-targeted therapy is an area of growing interest and holds promise for the treatment of solid tumors. Upon systemic administration, various types of non-pathogenic obligate anaerobes and facultative anaerobes have been shown to infiltrate and selectively replicate within solid tumors. The tumor specificity is based upon the unique physiology of solid tumors, which is often characterized by regions of hypoxia and necrosis. Prokaryotic vectors can be safely administered and their potential to deliver therapeutic proteins has been demonstrated in a variety of preclinical models. Although the amount of clinical experience with bacterial vectors is limited to date, the available data clearly demonstrated the feasibility of bacterial-mediated therapy in humans. There are several issues however that are still unknown and remain major challenges. In this review, using Clostridium and modified Salmonella as prototypical agents, we will discuss the major advantages, challenges and shortcomings of bacterial systems for tumor-specific therapy. In addition, we will highlight the requirements needed to advance the approach into clinical trials.

Enterobacterial tumor colonization in mice depends on bacterial metabolism and macrophages but is independent of chemotaxis and motility

“…In the past several years, cancer therapy with live bacteria has regained attention and significant advances have been achieved (Loeffler et al, 2007;Mengesha et al, 2007;Royo et al, 2007;Wei et al, 2007;Zhang et al, 2007).…”

Drug-inducible remote control of gene expression by probiotic Escherichia coli Nissle 1917 in intestine, tumor and gall bladder of mice

“…This provides new options for amelioration of metabolic disorders, allergies or autoimmune diseases [2,[8][9][10] but also for delivery of anticancer drugs and detection of residual cancerous tissue [11][12][13].…”

The bacterial ghost platform system

“…"Safer" non-viral systems such as attenuated bacteria, polycation/ DNA complexes, nucleoporation have reduced transfection efficiencies. [60][61][62][63][64][65][66][67] The BG system represents an alternative to current viral and bacterial methods in vaccine development with a new highly efficient gene delivery platform. One of the biggest advantages of the new DNA-carrier system is the safety of BGs.…”