Trojan Circulating Tumor Cells for Solid Tumor Infiltration
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Solution Overview
Problem
Immunotherapy faces challenges in addressing solid tumors due to tumor micro-environment defenses, such as immunosuppression at CTLA-4 and PD-1 checkpoints, CD38 enzymatic activity, and Galectin-1 overexpression, which hinder the effectiveness of current cancer treatments.
Innovation Solution
The method involves extracting and isolating circulating tumor cells (CTCs) from cancer patients, genetically engineering them to produce immune-stimulating exosomes, and administering these engineered CTCs or exosome-loaded dendritic cells back to the patient to bypass tumor defenses and stimulate a localized or systemic immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immunotherapy is used to treat solid tumors, then treatment effectiveness is limited, but the tumor micro-environment defense mechanisms remain active
Solution Approach 1:
The patent uses exosomes as intermediary carriers delivered by circulating tumor cells to transport immune-stimulating molecules into dendritic cells. These exosomes act as mediators that bypass the tumor micro-environment's defensive barriers and deliver therapeutic cargo to immune cells, thereby overcoming the harmful defense mechanisms while maintaining treatment effectiveness.
Solution Approach 2:
The patent exploits the ability of circulating tumor cells to replicate and circulate throughout the body, copying their invasive and evasive properties. By engineering these CTCs to produce immune-stimulating exosomes, the therapy leverages the natural replicative and migratory capabilities of tumor cells to distribute therapeutic agents widely throughout the tumor micro-environment, overcoming local defenses.
2Reliability
If treatment resistant circulating tumor cells are isolated and engineered, then immune stimulation is enhanced, but the complexity of the treatment process increases
Solution Approach 1:
The patent extracts and isolates circulating tumor cells from patient blood, then separates treatment-resistant subpopulations based on their differential response to anti-cancer agents. This extraction of specifically resistant cells enables targeted engineering to produce immune-stimulating exosomes, enhancing immune response while managing complexity through selective isolation rather than treating all tumor cells uniformly.
Solution Approach 2:
The patent modifies the genetic parameters of treatment-resistant circulating tumor cells by introducing genes that enable exosome production of immune-stimulating molecules. This parameter change transforms the engineered cells into therapeutic agents that can overcome tumor defenses, balancing the increased complexity of genetic engineering with the potential for enhanced therapeutic efficacy.
3Reliability
If genetically engineered circulating tumor cells are administered, then treatment resistance is overcome, but the risk of tumor cell infiltration increases
Solution Approach 1:
The patent converts the harmful invasive and infiltrative properties of circulating tumor cells into beneficial therapeutic effects. By engineering these cells to produce immune-stimulating exosomes, the therapy harnesses their natural ability to penetrate and circulate through tissues to deliver immune stimulation precisely where tumor cells are present, thereby overcoming treatment resistance while using their infiltration capability for therapeutic benefit rather than harm.
Data Source
AI summary
Provided herein are compositions and methods for engineering treatment resistant circulating tumor cells to generate immune stimulating or anti-cancer exosomes, which can be infused into a patient to self-home to the primary tumor and metastatic lesions. Also provided are compositions and methods for forming a population of engineered exosome-loaded dendritic cells, which can be infused into the patient to activate a systemic immune response. The compositions and methods allow for infiltration into solid tumors using “trojan” cells that are naturally adapted and mechanistically engineered to evade patients' defenses.