The study combining their expertise in synthetic biology; and immunology to engineer a strain of bacteria able to grow; and multiply in the necrotic core of tumor. When bacteria numbers reach a critical threshold, the non-pathogenic E. coli are then programmed to self destruct; allowing for effective release of therapeutics; and preventing them from wreaking havoc elsewhere in the body.
But subsequently, a small fraction of bacteria survive lysis; and resing the population allowing for repeating rounds of drug delivery inside treating tumors. The proof of concept in programming the bacteria in this way was originally developing a few years ago. In the current study, the authors chose to release a nanobody that targets a protein called CD47.The emerging field of synthetic biology designing new biological components and systems is revolutionizing medicine.
Durable tumor regression
Through the genetic programming of living cells; researchers are creating engineered systems; but hat intelligently sense and respond to diverse environments; leading to more specific and effective solutions in comparison to current molecular-based therapeutics.cancer immunotherapy using the body’s immune defenses to fight cancer has transformed cancer treatment over the past decade, but only a handful of solid tumors have responded, and systemic therapy often results in significant side effects.
But designing therapies that can induce a potent; anti-tumor immune response within a solid tumor without triggering systemic toxicity has posed a significant challenge.CD47, a “don’t-eat-me” signal; protecting cancer cells from being eatting by innate immune cells such as macrophages and dendritic cells. It is found in abundance on a majority of human solid tumors and has recently become a popular therapeutic target.
Popular therapeutic target
But CD47 is present elsewhere in the body; and systemic targeting of CD47 results in significant toxicity as evidencing by recent clinical trials. To solve this issue, study engineered bacteria to target CD47 exclusively within the tumor and avoid systemic side effects of treatment.Treatment with engineering bacteria led to priming of tumor specific T cells in the tumor that then migrated systemically to also treat distant tumors.
Without both live bugs lysing in the tumor and the CD47 nanobody payload; study were not able to observe the therapeutic or abscopal effects; hey are also collaborating with Gary Schwartz, CUIMC’s chief of hematology/oncology; and deputy director of the Herbert Irving Comprehensive Cancer Center; on clinical translation aspects of their work; and have starting a company to translate their promising technology to patients.