Phage Display Isolation of VHH Antibodies Targeting Capsular Polysaccharides of Intratumor Bacteria.

Phage display, a well-established and powerful tool, has been used to identify and isolate antibody fragments against a range of diverse cancer-related antigen types. Nonetheless, the availability of specific antibodies and antibody fragments against carbohydrate antigens remains low and insufficient. Bacteria found within cancer and immune cells affect tumorigenesis, progression, and shaping of the immunosuppressive microenvironment. Yet, their identification primarily relies on nucleic acid-based sequencing techniques at the species level, leaving a significant gap in molecular tools that distinguish bacterial strains and serotypes. This chapter provides a comprehensive protocol for phage display-based VHH antibodies identification against the capsular polysaccharides that define bacterial serotypes based on their composition and structure. We aim to illuminate a path for developing antibody fragments that will enable the targeting of specific intracellular bacterial strains and serotypes in tumor and immune cells, thereby unraveling their role and contribution to cancer biology.