For the contribution, we finalized the design of five parts for the remediation of acidic tumor microenvironment that causes noninflammatory polarization of tumor associated macrophages. In this year, three of the five parts have been tested on E. coli nissle 1917 for targeting tumor CSPG4 and CD47, and sensing environmental pH. We hope to make some contributions helpful for other people working in this field.

Designed five parts include

(1) Monoclonal antibody scFv-Fc is designed for the recognition of surface proteoglycan chondroitin sulfate proteoglycan 4 (CSPG4) on triple negative breast cancer (TNBC) cells. With the expression of monoclonal antibody scFv-Fc, engineered bacteria shall specifically target and move toward TNBC tumor cells.
(2) Fusion protein SIRPαD1-Fc is designed to compete with signal-regulatory protein alpha (SIRPα) on macrophage that can recognize and interact with cluster of differentiation 47 (CD47) on TNBC cells. It shall facilitate the phagocytic and cytotoxic activities of macrophages against TNBC tumor cells.
(3) Monocarboxylate transporter 1 (MCT1) is designed for the transportation and cleaning of lactate through bacteria TCA cycles.
(4) Acid inducible P-asr promoter that is induced by low pH less than 6.5 is designed for the stimulation of the expression of functional scFv-Fc and SIRPαD1-Fc in the acidic microenvironment.
(5) Base inducible P-atp2 promoter that is induced by high pH more than 6.5 is designed for the expression of self-clearance genes. When lactate is cleaned away from the microenvironment of tumors and the mission is completed, bacteria can be cleared by themselves.

Mathematic models, imaging techniques, portable photoacoustic device, software, computer programs, educational and social services were contributed to raise public awareness for early detection and prevention of triple negative breast cancer.