Researchers engineered bacteria to release chemokines into tumors to stimulate a stronger immune response.
Researchers at the Department of Microbiology and Immunology, Columbia University (NY, USA) have engineered bacteria with the capacity to alert the body to tumors and initiate tumor destruction. The bacteria release chemokines that attract ‘killer’ T cells and dendritic cells into the tumor, harnessing the host’s natural antitumor immune response. The scientists hope that this approach could develop into a new way to target cancers.
Scientists have been aware for several years that certain species of bacteria accumulate inside tumors. It is thought this is due to the low pH and necrotic environment at the core of the tumor microenvironment, providing the conditions for bacteria to grow, along with the lack of immune cells preventing their clearance.
In this paper, the researchers adapted a previously developed approach in which a non-pathogenic strain of Escherichia Coli bacteria was engineered to have a synchronized lysis circuit. This means that once a quorum of bacteria accumulates inside a tumor, this triggers the majority of the bacteria to lyse, releasing their contents.
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Senior author, Nicholas Arpaia commented, “although T cell responses that are specific to tumor-derived antigens are primed, sometimes what will happen is that despite there being primed antitumor T cells, they fail to be recruited into the tumor environment.” For this study, researchers engineered a strain of bacteria to produce CXCL16, a human chemokine that is known to attract activated T cells.
The researchers tested the efficacy of the engineered bacteria in vivo using various mouse models of cancer. They initially tested intratumoral injections of the bacteria for a total of four treatments delivered every 3–4 days. They subsequently assessed the systemic antitumor response generated by analyzing the effect of the injections on more distant tumors that had not been injected directly with the bacteria.
The results showed that engineered bacteria induce an immune response against both directly injected and distant tumors. The researchers found that this effect was mediated by CD8+ T cells and the effect was increased when a second strain of bacteria producing chemokines to attract dendritic cells was introduced.
“What we see is that the bacteria will only colonize the tumor environment, and they only reach a sufficient level of quorum to induce lysis within the tumor, so we can’t detect bacteria in other healthy organs,” explained Arpaia.
The team has applied for a patent for their approach and is part of biotechnology company GenCirq, Inc (CA, USA) and will continue to optimize their system further. They plan to do more research to lay the groundwork for a future clinical trial.
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