A Shiga Toxin B-Subunit-Based Lectibody Boosts T Cell Cytotoxicity towards Gb3-Positive Cancer Cells

Area of Science:

• Oncology
• Immunology
• Biotechnology

Background:

• Aberrant glycosylation is key in tumor progression and invasiveness.
• Tumor-associated carbohydrate antigens (TACAs) are promising immunotherapy targets.
• Glycan structures often have poor immunogenicity, necessitating improved targeting methods.

Purpose of the Study:

• To develop a novel lectibody for selective targeting of globotriaosylceramide (Gb3)-positive cancer cells.
• To evaluate the efficacy of the lectibody in redirecting T cell-mediated cytotoxicity against cancer cells.

Main Methods:

• Production and purification of a dimeric Shiga toxin B-subunit (StxB)-scFv UCHT1 lectibody in E. coli.
• Assessment of lectibody specificity for Gb3 on cancer cells and CD3 on T cells using flow cytometry.
• Evaluation of T cell-mediated cytotoxicity against Gb3-overexpressing cancer cells in vitro assays.

Main Results:

• The StxB-scFv UCHT1 lectibody demonstrated specificity for Gb3.
• The lectibody successfully redirected T cell cytotoxicity, leading to the killing of up to 80% of Gb3-overexpressing cancer cells.
• Efficacy was observed in both haemorrhagic and solid tumor models.

Conclusions:

• The developed lectibody shows potential for targeting Gb3-positive cancers.
• Lectibodies and lectins offer a promising approach to enhance immunotherapeutic strategies.
• This technology could improve the efficacy of existing cancer treatments.