Prostate cancer in situ autovaccination with the intratumoral viral mimic poly-ICLC: Modulating the cold tumor microenvironment.
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Nair Sujit S, Chakravarty Dimple, Balan Sreekumar, Hakansson Alexander, Duval Manuel, Davicioni Elai, Liu Yang, Bhardwaj Swati, Thin Tin Htwe, Garcia-Barros Monica, Haines Kenneth, Al Shaarani Majd, Weil Rachel, Meseck Marcia, Ratnani Parita, Fatterpekar Monali, Gonzalez-Gugel Elena, Farkas Adam, Wagaskar Vinayak, Jambor Ivan, Schlussel Kacie, Pasat-Karasik Cristina, Bhatt Kamala, Dovey Zachary, Pedraza Adriana, Gupta Akriti, Lundon Dara, Peros Ante, Parekh Sneha, Davenport Lily, Zhang Xiangfu, Gupta Raghav, Robison Macy, Knauer Cynthia, Ellis Ethan, Rykunov Dmitry, Reva Boris, Padanilam Babu, Galsky Matthew D, Brody Rachel, Menon Mani, Salazar Andres M, Bhardwaj Nina, Tewari Ashutosh K
Аннотация
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 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.
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.