Isogeneic Trop-2 Model for Evaluating Anti-Trop-2 ADCs

Antibody-Drug Conjugates (ADCs) have made significant advancements in cancer treatment, particularly for solid tumors. The bystander effect of ADCs, where cytotoxic payloads released by antibodies diffuse and kill nearby tumor cells, is a crucial mechanism, particularly in heterogeneous tumors where not all cells express the target antigen. This effect can enhance ADC efficacy, especially when some tumor cells lack the antigen.

Trophoblast cell surface antigen 2 (Trop-2) is a cell surface glycoprotein that is often overexpressed in various cancers.  Trop-2 is a target for cancer therapy because of its high expression in many epithelial tumors while being present at lower levels in normal tissues. Trop-2 plays a role in tumor growth, invasion, and metastasis, making it a promising target for ADCs.

At AACR 2025, WuXi Biology presented a poster describing the development of an isogeneic Trop-2 expression heterogeneity model.  The authors show that this model provides an effective platform for evaluating the bystander killing activity of anti-Trop-2 ADCs. Both in vitro and in vivo experiments demonstrated significant bystander killing effects, validating the potential of anti-Trop-2 ADCs in treating tumors with heterogeneous antigen expression.

AACR 2025 Poster_Isogeneic Trop-2 Model for Evaluating ADCs

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