Prostate cancer in situ autovaccination with the intratumoral viral mimic poly-ICLC: Modulating the cold tumor...

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.

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.

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 PSA₀ (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.

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.

This work was funded by the Arthur M. Blank Family Foundation.