Therapeutic Immune Modulation Against Solid Cancers with Intratumoral Poly-ICLC: A Pilot Trial
Abstract
Purpose: Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (poly-ICLC), a synthetic double-stranded RNA complex, is a ligand for toll-like receptor-3 and MDA-5 that can activate immune cells, such as dendritic cells, and trigger natural killer cells to kill tumor cells. Patients and Methods: In this pilot study, eligible patients included those with recurrent metastatic disease in whom prior systemic therapy (head and neck squamous cell cancer and melanoma) failed. Patients received 2 treatment cycles, each cycle consisting of 1 mg poly-ICLC 3× weekly intratumorally (IT) for 2 weeks followed by intramuscular (IM) boosters biweekly for 7 weeks, with a 1-week rest period. Immune response was evaluated by immunohistochemistry (IHC) and RNA sequencing (RNA-seq) in tumor and blood. Results: Two patients completed 2 cycles of IT treatments, and 1 achieved clinical benefit (stable disease, progression-free survival 6 months), whereas the remainder had progressive disease. Poly-ICLC was well tolerated, with principal side effects of fatigue and inflammation at injection site (<grade 2). In the patient with clinical benefit, IHC analysis of tumor showed increased CD4, CD8, PD1, and PD-L1 levels compared with patients with progressive disease. RNA-seq analysis of the same patient's tumor and peripheral blood mononuclear cells showed dramatic changes in response to poly-ICLC treatment, including upregulation of genes associated with chemokine activity, T-cell…
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