• Engineered Bacteria as a Versatile Platform in Cancer Therapy
  • Mozhdeh Mahmoudabadi,1 Saman Hakimian,2,*
    1. Student of Microbiology Islamic Azad University of Mashhad
    2. M.sc student of Pathogenic Microbes Islamic Azad University Central Tehran Branch


  • Introduction: Cancer remains one of the leading causes of death worldwide. Despite extensive research efforts and recent advancements in treatment methodologies, each approach carries specific limitations, resulting in millions of cancer-related deaths annually. Recently, bacteria have gained attention as versatile platforms that can enhance tumor detection and treatment, either as standalone agents or in combination with other therapies. Genera such as Salmonella, Escherichia, and Clostridium are known for possessing these beneficial properties. These microorganisms can be genetically engineered to deliver various therapeutic payloads locally within the tumor and its microenvironment. Furthermore, advancements in synthetic biology and genetic circuit design enable researchers to control bacterial behavior, tailoring the release of therapeutics to occur at specific times and locations. By leveraging techniques such as mutagenesis and genetic engineering, bacteria can link their growth to environmental signals from tumors, enhance their adhesion to cancer cells, and specifically amplify their growth in hypoxic areas—potentially increasing their proliferation up to 10,000-fold in these environments.
  • Methods: The transfer of these molecules can occur through methods such as passive diffusion, transport across microbial and mammalian membranes, or by utilizing secretion systems like the Type III secretion system (T3SS). This system, present in Gram negative bacteria, secretes effective macromolecules into host cells using a needle-like complex. Moreover, engineered bacteria can modulate tumor metabolism, such as converting ammonia to L-arginine, which facilitates increased infiltration of lymphocytes within the tumor. Collectively, these approaches underscore the significant potential of engineered bacteria in cancer therapy by programming immune responses. Additionally, bacteria can work synergistically with external materials and technologies. External interventions, such as ultrasound and magnet-based approaches, can enhance bacterial behavior, allowing for tumor visualization and remote control, which can precisely adjust the location and timing of therapeutic release within the tumor. Integrating imaging techniques like MRI, PET, and focused ultrasound (FUS) also permits the tracking and visualization of delivered bacteria. By encoding bacteria with reporter genes or thermal switches, FUS can be utilized to trigger therapeutic release upon activation. Drugfilled nanoparticles canphysically conjugate with bacteria, enabling transportation to deep regions of tumors that may otherwise be inaccessible. The magnetic properties of certain bacteria also offer innovative approaches to cancer treatment. For example, engineered bacteria can be programmed to eliminate other bacterial strains that interfere with chemotherapy effectiveness.
  • Results: These challenges must be carefully addressed and managed in order to achieve higher efficacy and safety in bacterial-based cancer therapies.
  • Conclusion: Finally, although significant progress has been made in the development of bacterial cancer treatments, there are concerns in various areas, such as: 1. The degree of bacterial efficacy in tumor tissue at early stages. 2. The possibility of genetic mutations in bacteria and the loss of therapeutic agents. 3. Immune responses such as bacteremia and cytokine storms. 4. The limited effectiveness of bacteria under environmental conditions, such as temperature and pH.
  • Keywords: Engineered bacteria, Cancer therapy, Tumor microenvironment, Synthetic biology