Developing a tumor-selective antibody Fc region to redirect the immune system to attack cancer cells

Abstract Cancer is a leading cause of death worldwide and rates of cancer are increasing over time. Immunotherapeutics are a growing field of anti-cancer treatments that use the immune system to target tumor cells. Many immunotherapies use biomarker targeting, however biomarkers are present on healthy tissues which can lead to off-tumor effects and mutations in biomarkers can cause patients to become non-responsive to targeted immunotherapies. Most tumors exhibit acidosis due to the Warburg effect so low pH provides a potential target for immunotherapy. This research uses a pH low-insertion peptide (pHLIP) conjugate to target cancer cells. pHLIP is conjugated to the antibody Fc region for immune system recruitment, simplifying the immunotherapy approach by eliminating the need for antibody-antigen recognition.