Way back in 1890, William Coley, a young cancer surgeon, noticed that dozens of cancer patients had a regression of their disease while carrying a separate infection. This raised a significant question: While fighting against bacterial infection, can the human body simultaneously battle a tumor?
Researchers found the answer when tumor shrinkage was noticed after injecting bacteria into nearly a thousand patients with varying degrees of success.
This ability to modulate the body's immune response and behavior, by applying engineering principles to biology forms the basis of Synthetic Biology. This technology is ushering in a new era of cancer therapy and changing the landscape of healthcare. Genetic reprogramming of immune cells and safer immune-therapeutics are two main focus of synthetic biology in cancer therapy.
Can bacteria cure cancer?
Engineering of bacteria for immune-cancer therapy using synthetic biology is an upcoming trend. This involves various treatment aspects such as therapeutic, safety, and specificity features through genetic modification. Developments in genetic reprogramming include targeting bacteria to tumors, specific sensing and response to tumor microenvironments, remote induction methods, and controllable release of therapeutics.
Synthetic biology capitalizes on bacteria's natural ability to colonize immunoprivileged, hypoxic core regions of tumors by escaping from leaky vasculature. A variety of strategies such as targeting, inducing gene expression, quorum-sensing, expressing and releasing cytotoxics, and intracellular gene delivery have been engineered to control these bacteria's behavior and produce anti-tumor effects.
Cancer startups with a bold twist
Synlogic is preparing to transform cancer management by introducing live, engineered bacteria as a cancer drug. Their lab results have shown that mice injected with engineered, live bacteria SYNB1891 could shrink cancer tumors. The treatment also appeared to provide mice with long-term protection in the form of immune memory. Promisingly, treatment of human cells with SYNB1891 led to a similar stimulation of the immune response as seen in mouse models, providing a positive indication for humans' success.
Targeted vaccines and cancer immunotherapies using synthetically engineered bacteria are available at Prokarium. This microbial cancer immunotherapy uses Onconella™ strain, a particular bacterium developed by the company, acts by identifying the solid tumor, targeting it, and then colonizing it to exert its therapeutic effect.
Ideaya Biosciences is an oncology-focused startup aiming to discover breakthrough synthetic lethality medicines for genetically defined patient populations and immuno-oncology therapies targeting immuno-metabolism and innate immunity.
Poseida Therapeutics uses gene-editing techniques to develop treatments for multiple myeloma and prostate cancer, among other conditions. These work by harnessing the power of a patient's own immune system for the treatment of cancer. It is aimed to result in safer, more effective, accessible, and affordable remedies for patients in need.
Tango Therapeutics uses technology like CRISPR to genetically edit immune cells such as T cells and infuse them back into the patients for cancer treatment.
OncoOne develops drugs that target an oxidized version of an immune protein called macrophage migration inhibitory factor (oxMIF), which is only present in diseased tissue that can be used in cancer treatment.
Sana Biotechnology designs cells to treat cancer, central nervous system diseases, heart disease, and genetic disorders. These specialized cells can function in a variety of ways, depending on the application. For instance, some might replace damaged or missing cells in the body, while others deliver molecular payloads of RNA, DNA, or proteins to reprogram existing cells.
ArsenalBio is focused on integrating technologies such as CRISPR-based genome engineering, scaled and high throughput target identification, synthetic biology, and machine learning to advance a new paradigm to discover and develop in immune cell therapies. The potential applications of CRISPR are enormous. It's the closest stage to a cure for cancer. Using this technology, HIV infection in animal models and even human cell cultures has been cured by removing the viral genes that insert themselves into our DNA.
Kite Pharma offers innovative cancer immunotherapy through re-engineered chimeric antigen receptor and t-cell receptor therapy, capable of boosting the patient's immune system's ability to recognize and kill tumors.
ZIOPHARM Oncology employs novel cell engineering techniques and multigenic gene programs to develop next-generation patient- and donor-derived adoptive cellular therapies based on designer cytokines, such as genetically modified T cells and NK cells, to target hematologic malignancies and solid tumors as well as graft-versus-host-disease. These technologies are designed to improve safety and decrease the cost, time, and complexity of development associated with cell-based therapies.
Better future with better therapy
Cancer immunotherapy has come a long way. Treatment options are now available that use antibodies to target specific proteins of cancer. These antibodies come as drugs, vaccines, or immune cell infusions, and they work to enable the body's natural defenses to fight cancer naturally. Synbio in cancer therapy takes advantage of both biotechnology and the human body's unique immune capabilities. It gives the clinician the capacity to deliver wave after wave of immune response from a single treatment utilizing synbio. However, currently, there are challenges, such as genetic stability, that researchers must address to successfully implement this novel therapy in humans.
The ultimate goal would be to deliver targeted genetic material in vivo and ex vivo gene therapies to redefine disease treatment.