Bacteriophages as Solid Tumor Theragnostic Agents

Abstract

Cancer, especially the solid tumor sub-set, poses considerable challenges to modern medicine owing to the unique physiological characteristics and substantial variations in each tumor's microenvironmental niche fingerprints. Though there are many treatment methods available to treat solid tumors, still a considerable loss of life happens, due to the limitation of treatment options and the outcomes of ineffective treatments. Cancer cells evolve with chemo- or radiation-treatment strategies and later show adaptive behavior, leading to failed treatment. These challenges demand tailored and individually apt personalized treatment methods. Bacteriophages (or phages) and phage-based theragnostic vectors are gaining attention in the field of modern cancer medicine, beyond their bactericidal ability. With the invention of the latest techniques to fine-tune phages, such as in the field of genetic engineering, synthetic assembly methods, phage display, and chemical modifications, noteworthy progress in phage vector research for safe cancer application has been realized, including use in pre-clinical studies. Herein, we discuss the distinct fingerprints of solid tumor physiology and the potential for bacteriophage vectors to exploit specific tumor features for improvised tumor theragnostic applications.

Keywords: bacteriophages; theragnostics; tumor.

Figure 1

Solid tumor’s microenvironmental architecture.

Figure 2

Challenges faced by cancer therapeutic bacteriophage vectors in biological systems.

Figure 3

In vivo treatment of chondrosarcoma SW1353-bearing mice with intravenous administrations of RGD4C/H5W-Phage-sTNFα. Tumor-bearing mice were intravenously injected with RGD4C/H5W-Phage-sTNFα or non-targeted H5W-Phage-sTNFα vector. (A) Representative tumor-bearing mice imaged using the in vivo Bioluminescent Imaging System at day 0, before treatment initiation, and day 14, post-vector administration. (B) Average tumor volumes progression in each experimental group. (C) The luminescence values of tumors shown as fold change between pre-treatment day 0 and post-vector treatment day 14. (D) Average weights of SW1353 tumor-bearing mice. Adapted with permission from FASEB. * p < 0.05.

Figure 4

A schematic summary of the breast cancer vaccine study (gpD::GP2) in a TUBO tumor model of BALB/c mice. Adapted with permission from NPG. * p < 0.05, ** p < 0.01 and **** p < 0.0001; denotes significant difference from the control groups.