T-cell Engagers in Prostate Cancer

Owing to the “cold” tumor immune microenvironment of prostate cancer, immune-targeting agents have shown limited efficacy in patients with advanced prostate cancer, highlighting the need for new therapies with novel mechanisms of action. In this context, T-cell engagers (TCEs), which induce T-cell–mediated killing of cancer cells by binding the CD3 receptor on T cells and a specific tumor antigen expressed on malignant cells, represent a promising therapeutic option. Multiple studies have explored the use of TCEs in previously treated patients with metastatic castration-resistant prostate cancer, and several ongoing trials are currently assessing novel TCEs either as single agents or in combinatorial regimens with molecules with a distinct mechanism of action (eg, androgen receptor pathway inhibitors and other immune-targeting agents). Although TCEs have shown promising antitumor activity with prostate-specific antigen and radiographic responses, they still face considerable challenges that prevent their implementation into clinical practice. These include their immunogenicity and the development of antidrug antibodies, which could impact their serum drug exposure, as well as their toxicity profile involving cytokine release syndrome and other immune-related adverse events. To improve their efficacy and pending the results of ongoing trials, there could be a role for combinatorial regimens, administration in earlier lines of therapy, and biomarker-driven selection.