The local problem

The Challenge: Overcoming Triple-Negative Breast Cancer Triple-Negative Breast Cancer (TNBC) is a particularly aggressive subtype of breast cancer, characterized by the absence of estrogen, progesterone, and HER2 receptors. This lack of targets renders many common hormonal therapies ineffective, leaving patients with fewer, often more aggressive, treatment options like chemotherapy, which can have significant side effects. A primary obstacle in fighting TNBC is the sophisticated defense system it builds around itself, known as the Tumor Microenvironment (TME). The TME suppresses the body's natural immune response, creates its own blood supply to fuel its growth, and effectively hides from immune cells that would otherwise destroy it. Our project directly confronts these challenges with a dual-action system designed to first identify the tumor non-invasively and then systematically break down its defenses. .

Inspirations

Our Solution: A Two-Phase Approach to Diagnose and Weaken Our project is built on a two-phase strategy: first, to accurately detect the tumor's location, and second, to make it susceptible to the body's immune system. Phase 1: A Fluorescent Tag for Non-Invasive Diagnosis The first component of our system is a precision-guided diagnostic tool. We have engineered a molecular "tumor tag" with high specificity for the HN-1 protein, a molecule known to be abundant in the TME of TNBC. This tag is fused to a Red Fluorescent Protein (RFP). When introduced into the body, this construct circulates until it locates and binds to the HN-1 proteins within the TME. The accumulation of our tag in the cancerous region results in a concentrated fluorescent signal, allowing for the precise, visual identification of the tumor's location without the need for an invasive and often painful biopsy. This provides a safer, faster, and more patient-friendly method for initial diagnosis and monitoring.

Phase 2: Dismantling the Tumor's Fortress to Empower T-Cells Once the tumor is located, the second phase of our project begins: weakening its defenses. We are targeting three of the most critical pillars that support the tumor's survival and growth. Our therapeutic design aims to simultaneously inhibit these pillars: Anti-VEGF (a-VEGF): Tumors require a constant supply of nutrients and oxygen to grow, which they acquire by stimulating the formation of new blood vessels (angiogenesis). Our system includes an anti-VEGF component to block this process, effectively cutting off the tumor's supply lines and stifling its growth. .

Anti-CTLA-4 (a-CTLA-4): T-cells are the primary soldiers of our immune system. However, molecules like CTLA-4 act as "brakes" that prevent T-cells from activating and attacking. Our system introduces an anti-CTLA-4 agent to release this brake, allowing a more powerful and widespread T-cell response against the cancer. Anti-PD-1 (a-PD-1): To survive, tumor cells often display the PD-L1 protein on their surface, which connects to the PD-1 receptor on T-cells. This interaction signals the T-cell to stand down, effectively cloaking the tumor from immune attack. By introducing an anti-PD-1 component, we block this connection, unmasking the tumor cells and making them visible and vulnerable to attack by the now-active T-cells.

By launching this coordinated, three-pronged attack on the tumor microenvironment, our project does not aim to kill the cancer cells directly. Instead, it strategically weakens the tumor and dismantles its defenses, clearing the way for the body's own natural T-cells to do their job. This approach promises to dramatically increase the success rates and safety of current treatments, creating a powerful synergy between our synthetic biology system and the patient's natural immunity.