Therapeutic immune modulation against solid cancers with intratumoral poly-ICLC: a pilot trial
Clinical Cancer Research, 2018•AACR
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 …
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 …
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 (
Conclusions: Poly-ICLC was well tolerated in patients with solid cancer and generated local and systemic immune responses, as evident in the patient achieving clinical benefit. These results warrant further investigation and are currently being explored in a multicenter phase II clinical trial (NCT02423863). Clin Cancer Res; 24(20); 4937–48. ©2018 AACR.
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