(A) Illustration of the migration of cargo-carrying tumor-tropic bacteria toward a tumor. The outer cells (dark blue) are proliferating cells. The green cells represent dormant cancer stem cells (CSCs). Note that in real tumors the fraction of this subpopulation of cells is very low, and they can be widely scattered. The red cells are necrotic cells, and the light blue cells are stromal cells (see Ben-Jacob et al4 for more details). (B) Illustration of cargo-carrying Trojan-horse bacteria engineered to express antibodies targeting the tumor-specific antigens. This recognition enables the bacteria to enter the cells and inject the antitumor cargo.
The use of creativity in developing treatment options for cancer is a necessity, as cancer is one of the most difficult diseases to treat with traditional techniques, without causing harm to the patient. One could argue that using a deadly strain of bacteria to fight cancer is as creative as it gets. Specifically, Massa et al. at the European Institute of Oncology have demonstrated that Salmonella, a facultative anaerobic strain of gram-negative bacteria, can be engineered to deliver the herpes simplex virus thymidine kinase (anti-tumor cargo) locally to tumor cells. This is partially facilitated by the Warburg effect, which is an observation that tumor cells tend to rely on high rates of glycolysis (anaerobic) rather than aerobic respiration, as in normal cells. Hence, the engineered bacteria can successfully invade tumor cells, and deliver their cancer-killing cargo.
As if this were not brilliant enough, the engineered Salmonella can also teach the patients’ own T-cells to successfully target cancer cells. The Salmonella can cause the innate immune system (dendritic cells) to form gap junctions (cytoplasmic pathways) with the cancer cells. Thus, the dendritic cells use peptides transferred from the cancer cells to create antigens, so that the adaptive immune system may eliminate the cancer at the primary site, as well as to prevent metastasis. This research into cancer treatment is an insightful look into the potential future of cancer-warfare, where cancer killing bacteria fight alongside the immune system, greatly minimizing further harm to the patient.
From Blood:
“The engineered bacteria can then kill the cancer cells directly or expose them to the immune system and to other recruited bacteria engineered to kill them by acting together with the immune system. For example, it is now understood that most tumors at advanced stages are composed of several subclones. We can foresee the engineering of several Trojan-horse bacteria acting together, each able to better identify and target a specific clone. We may be seeing here the dawning of a new era of biological cyberwarfare on cancer, in which we willenlist bacteria to fight with the immune system and defeat cancer with minimal side effects to the patients.”
Article: Engineering Trojan-horse bacteria to fight cancer…
Study abstract in journal Blood: Salmonella engineered to express CD20-targeting antibodies and a drug-converting enzyme can eradicate human lymphomas
