A Trojan horse for a tumor
The development of cancer treatments that trigger a powerful, but non-toxic, antitumor immune response is a significant challenge.
To solve it, scientists from Columbia University combined their knowledge in the field of synthetic biology and immunology and created a strain of non-pathogenic bacteria Escherichia coli, which can colonize solid tumors in mice and safely deliver potent drugs, penetrating the tumor like a Trojan horse to destroy it from the inside. Such a method led not only to complete regression of lymphoma in mice, but also to significant control of distant tumor lesions. This is the first evidence of the so-called abscopic effect using bacterial therapy.
Now it becomes possible to create bacteria for local destruction of tumors, and then stimulate the immune system to search for these tumors and metastases that are too small to detect using imaging or other methods.
A new strain of bacteria, capable of growing and multiplying in the necrotic nucleus (or in the dead zone) of tumors. Such bacteria are programmed to self-destruct when their number reaches a critical threshold, which makes it possible to effectively release drugs and prevent their destruction in other parts of the body. A small part of the bacteria survives after lysis and forms new colonies, which makes it possible to repeatedly deliver drugs inside tumors.
The proof of effectiveness of the bacterial programming concept was originally developed three years ago (Din et al., Nature 2016).
In the current study, a nanotele aimed at a protein called CD47 was used to fight cancer cells. CD47 sends a "don't eat me" signal to immune cells, thus protecting cancer cells from macrophages and dendritic cells. The protein is found in abundance on most solid human tumors and has recently been a popular therapeutic target. But CD47 is not only present in tumor cells, so systemic targeting of this protein is highly toxic, as evidenced by recent clinical trials. The new strain of bacteria acts exclusively inside the tumor and does not cause systemic side effects, unlike other treatments.
The combined effect of bacterial-induced inflammation in the tumor and CD47 blockade leads to increased phagocytosis of tumor cells and, as a consequence, to increased activation and proliferation of tumor-specific T cells. In addition, it was found that this method of treatment reduces the frequency of metastasis formation,
Scientists are conducting further research in the field of safety and toxicology of immunotherapeutic bacteria. The positive results of these studies will lead to clinical trials in humans.
The article by Chowdhury et. al Programmable bacteria induce durable tumor regression and systemic antitumor immunity is published in the journal Nature Medicine.
Elena Panasyuk, portal "Eternal youth" http://vechnayamolodost.ru / based on Columbia Engineering: Bacteria Engineered as Trojan Horse for Cancer Immunotherapy.