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Background Neoadjuvant therapies for high-risk PCa have shown promise but remain confined to clinical trials. Translating neoadjuvant approaches into routine care thus underscores the critical need for innovative early-phase neoadjuvant trials to evaluate safety and efficacy in localized disease, where tumors are more responsive to intervention. Methods In this open-label phase 1 trial ( NCT03262103 ), 12 patients with clinically localized intermediate- to high-risk PCa scheduled for radical prostatectomy (RP) received sequential intratumoral and intramuscular injections of poly-ICLC (Hiltonol®), with the primary endpoint to define a safe dose and schedule and one of the secondary endpoints to characterize associated adverse events. Findings All patients tolerated poly-ICLC without dose-limiting toxicity or treatment withdrawal. Median follow-up was 4.5 years. Seventy percent of the evaluable patients had PSA 0 (measured as PSA <0.1 ng/mL) 1 year post-RP. Gleason score at final pathology was downgraded in 66.7% of all patients and 70% of the high-risk subgroup. Tissue transcriptomic analysis revealed decreased metastasis signature post-treatment, with upregulation of immune cell-related and favorable-prognosis genes. Intratumoral and intramuscular poly-ICLC also enhanced immune activation signatures in the blood and increased NK cells in both blood and tissues. Treatment increased post-treatment infiltration of CD4 + , CD8 + , and PD-1 + T cells; CD56 + NK cells; CD20 + B cells; and tertiary lymphoid structure-like aggregates. Conclusions Intratumoral poly-ICLC immunotherapy for PCa is safe and may modulate the tumor microenvironment, enhancing antitumor responses. These findings support larger, controlled trials to assess effects on long-term clinical outcomes. Funding This work was funded by the Arthur M. Blank Family Foundation.
Nair et al. (2025) studied this question.