pH-Dependent Grafting of Cancer Cells with Antigenic Epitopes Promotes Selective Antibody-Mediated Cytotoxicity

Area of Science:

• Oncology
• Immunology
• Biochemistry

Background:

• Current immunotherapies face limitations due to the lack of universal cancer biomarkers.
• Targeting specific tumor markers restricts treatment to a small patient subgroup.

Purpose of the Study:

• To develop a novel class of cancer therapeutics that target solid tumors universally.
• To exploit the unique acidic tumor microenvironment for selective cancer cell targeting.

Main Methods:

• Designed immuno-engager agents utilizing the pH-Low Insertion Peptide (pHLIP) for pH-dependent tumor cell surface anchoring.
• Conjugated pHLIP with antigens to create targeted epitopes.
• Assessed the ability of pHLIP-antigen conjugates to recruit immune cells and induce cytotoxicity.

Main Results:

• pHLIP-antigen conjugates selectively grafted cancer cells in a pH-dependent manner.
• These conjugates effectively recruited antibodies to the cancer cell surface.
• Demonstrated induction of cytotoxicity by peripheral blood mononuclear cells and engineered NK cells.

Conclusions:

• The developed agents offer a promising approach for treating a wide range of solid tumors.
• This strategy circumvents limitations associated with narrow tumor biomarker selectivity.
• Exploiting tumor acidity provides a universal targeting mechanism for immunotherapy.