ADCT-241: PSMA-Targeted Antibody–Drug Conjugate Shows Bystander Activity in Prostate Cancer Models

A new preclinical study published in Molecular Cancer Therapeutics reports encouraging results for ADCT-241, an experimental antibody–drug conjugate (ADC) designed to target prostate-specific membrane antigen (PSMA) in prostate cancer.

ADCT-241 combines a PSMA-targeting antibody with a cytotoxic payload derived from exatecan, a topoisomerase I inhibitor. Unlike PSMA-targeted radioligand therapies, which deliver radiation to tumour cells, this approach uses an antibody to transport a chemotherapy-like compound directly into PSMA-expressing cells.

The treatment demonstrated antitumour activity in prostate cancer cell lines and mouse models, including patient-derived tumour xenografts. Researchers also observed a bystander effect, in which the released cytotoxic compound damaged neighbouring PSMA-negative cells. This is particularly relevant because PSMA expression can vary considerably between tumour cells, potentially allowing some to escape PSMA-directed treatments.

The results suggest that ADCT-241 could offer a strategy for targeting tumours with heterogeneous PSMA expression.

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