Programmable Bacteria With Synchronized Lysis for Tumor Delivery
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Solution Overview
Problem
Current cancer treatments, such as chemotherapy and immune checkpoint inhibitors, suffer from non-specificity and severe side effects, and there is a need for controlled, localized delivery of therapeutic agents to tumor sites to minimize adverse effects and target difficult tumors.
Innovation Solution
Programmable bacteria engineered with a synchronized lysis circuit in a single operon or plasmid to produce therapeutic agents like nanobodies and toxins, which are delivered locally to tumors, minimizing systemic toxicity and enhancing immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint inhibitors are administered systemically to treat cancer, then antitumor efficacy is improved, but immune-related adverse effects increase
Solution Approach 1:
The patent applies local quality by delivering immune checkpoint inhibitors specifically to the tumor site through programmable bacteria that colonize tumors. The bacteria express the therapeutic agents locally, creating a concentrated treatment zone that improves antitumor efficacy while minimizing systemic exposure and associated adverse effects.
Solution Approach 2:
The patent uses programmable bacteria as an intermediary delivery system. These bacteria serve as vectors that carry and express immune checkpoint inhibitors at the tumor site, mediating the delivery of therapeutic agents directly to cancer cells while avoiding direct systemic administration and its harmful effects.
2Reliability
If chemotherapy is administered to treat cancer, then tumor growth is inhibited, but non-specificity and toxicity increase
Solution Approach 1:
The patent achieves local quality by using tumor-colonizing bacteria that naturally target cancerous tissue. The programmable bacteria accumulate in the tumor microenvironment and deliver therapeutic agents specifically where needed, avoiding the non-specific toxicity of conventional chemotherapy while maintaining effective tumor growth inhibition.
Solution Approach 2:
The patent applies self-service by utilizing the bacteria's inherent ability to colonize tumors and persist in the tumor microenvironment. This natural tropism for cancerous tissue provides autonomous targeting without requiring external guidance systems or causing off-target effects, thereby reducing non-specificity and toxicity.
3Reliability
If classic cancer treatments are used, then cancer is treated, but side effects are severe due to non-specificity
Solution Approach 1:
The patent implements local quality through spatially-controlled delivery of therapeutic agents via programmable bacteria. The bacteria establish presence and express therapeutic proteins specifically within the tumor site, creating a localized treatment effect that maintains cancer treatment efficacy while eliminating severe systemic side effects associated with non-specific treatments.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The programmable bacteria achieve localized delivery of therapeutic agents, reducing side effects and inducing systemic antitumor immunity, leading to tumor regression and abscopal effects without adverse reactions, and are effective against both primary and metastatic cancers.
Implementation Method 1
programmable bacteria comprising at least one synchronized lysis circuit contained in a single operon which are capable of being further engineered to cyclically produce anti-cancer therapeutic agents
Data Source
AI summary
Disclosed herein are programmable bacteria for tumor-targeted immunotherapeutic delivery. In certain embodiments, the programmable bacteria comprise at least one synchronized lysis circuit contained in a single operon which are capable of being further engineered to cyclically produce anti-cancer therapeutic agents including but not limited to nanobodies against immune checkpoint inhibitors and over-expressed markers in cancers, toxins, tumor antigens, cytokines, and chemokines. In some embodiments, the programmable bacteria comprise at least one synchronized lysis circuit contained in a single operon and at least one plasmid producing a therapeutic agent, i.e., at least one plasmid comprising a nucleic acid sequence which encodes a therapeutic agent. The disclosure also provides methods of curing and treating cancer using the programmable bacteria.