Therapeutic immune modulation against solid cancers with intratumoral poly-ICLC: A pilot trial

Chrisann Kyi, Vladimir Roudko, Rachel Sabado, Yvonne Saenger, William Loging, John Mandeli, Tin Htwe Thin, Deborah Lehrer, Michael Donovan, Marshall Posner, Krzysztof Misiukiewicz, Benjamin Greenbaum, Andres Salazar, Philip Friedlander, Nina Bhardwaj

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Purpose: Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (poly-ICLC), a synthetic double-strandedRNA 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 μg 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 activation, and antigen presentation. 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).

Original languageEnglish (US)
Pages (from-to)4937-4948
Number of pages12
JournalClinical Cancer Research
Volume24
Issue number20
DOIs
StatePublished - Oct 15 2018
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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